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88 results on '"Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed)"'

1. Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) under managed care: a clinical and environmental investigation in a French zoological park

Author: Estelle Cateau, Antoine Leclerc, Noémie Cartier, Isabel Valsecchi, Éric Bailly, Ronan Le Senechal, Margaux Becerra, Brice Le Gallou, Rose-Anne Lavergne, Adélaïde Chesnay, Jean-Patrice Robin, Carolyn Cray, Nicolas Goddard, Milan Thorel, Jacques Guillot, Baptiste Mulot, Guillaume Desoubeaux, Service de Parasitologie - Mycologie - Médecine Tropicale, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ZooParc de Beauval, Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Miami Leonard M. Miller School of Medicine (UMMSM), and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)
Subjects: Azoles, Antifungal Agents, MICs, microsatellite genotypin, Aspergillus fumigatus, Managed Care Programs, Microbial Sensitivity Tests, General Medicine, Spheniscidae, Fungal Proteins, Infectious Diseases, MESH: Spheniscidae, Drug Resistance, Fungal, birds, Mutation, [SDE]Environmental Sciences, Aspergillus nishimurae, cyp51A, Animals, Aspergillosis, Humans, MESH: Aspergillosis, azole-resistance, Humboldt penguins
Abstract: Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs. The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018–20: all isolates were counted and characterized by sequencing. When identified as Aspergillus fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for minimal inhibitory concentrations (MICs) determination. At the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains. Environmental investigations highlighted the substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and a large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains. Lay summary
Published: 2022

2. Aluminum exposure from food in the population of Lebanon

Author: Raed Ezzeddine, Mohamad Al Iskandarani, Sarine El Daouk, Mariam Taha, Alain Pineau, Akram Hijazi, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: inorganic chemicals, Acid digestion, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Population, 010501 environmental sciences, Toxicology, complex mixtures, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Animal science, lcsh:RA1190-1270, Flame atomic absorption spectrometry, Medicine, Ingestion, FAASs, education, lcsh:Toxicology. Poisons, 0105 earth and related environmental sciences, 2. Zero hunger, education.field_of_study, business.industry, Dietary exposure, Regular Article, Food safety, 3. Good health, E-FFQ, Ice cream, Provisional Tolerable Weekly Intake, Food matrix, Daily dietary exposure, business, 030217 neurology & neurosurgery, Aluminum, Contaminated food
Abstract: Highlights • Estimation of dietary aluminum rates in the Lebanese population. • Creation of food frequency questionnaire targeting aluminum. • Safety requirements and recommendations., Widely used for a variety of applications, levels of dietary aluminum (Al) have seen a perpetual rise in Lebanon, leading to noticeable effects upon the human body. This study aims to estimate the rates of Al contaminated food consumption and quantify the Al present in different dietary matrices, revealing the major contributors to Al exposure for the Lebanese population. A cross-sectional study was conducted using a customized, self-reported Electronic Food Frequency Questionnaire (E-FFQ) using Curve®, targeting individuals between the ages of 18 and 64 from different Lebanese regions, distributed proportionally. The selection of food was based upon the results of the French EAT2 study. Al levels in food were analyzed using Flame Atomic Absorption Spectrometry (FAAS) after acid digestion. The E-FFQ was completed by 167 respondents. Data analysis was performed on SPSS version 25. Additionally, 97 food items were studied in 2018. Al levels had a mean of 3.56 ± 2.08 mg/kg (ranging from 0.14 to 9.37). The highest Al levels were found in vegetables, followed by sauces and condiments, candies, and ready meals. The Provisional Tolerable Weekly Intake (PTWI) of Al was set at 0.50 mg/kg body weight (60 Kg/person). Al mean Daily Dietary Exposure (DDE) was estimated to be 4341.18 μg/day, with the highest food exposure coming from lettuce, soft drinks, ice cream and tea. Al ingestion rates for the adult Lebanese population does not exceed the international established thresholds of tolerable intake (1 mg/kg/week). National recommendation should be developed to control the presence of metal for food safety purposes.
Published: 2020

3. Comparison of MultiLocus Sequence Typing (MLST) and Microsatellite Length Polymorphism (MLP) for Pneumocystis jirovecii genotyping

Author: Stéphane Bretagne, Pascal Campagne, Patrice Le Pape, Maud Gits-Muselli, Marie Desnos-Ollivier, Alexandre Alanio, Florent Morio, Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), MGM’s salary was funded by Assistance Publique-Hôpitaux de Paris and Institut Pasteur (Poste d’ accueil APHP/CNRS/Institut Pasteur)., Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Cibles et Médicaments des Infections et de l'Immunité (IICiMed)
Subjects: Genotyping, lcsh:Biotechnology, Biophysics, Context (language use), MLP, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Structural Biology, lcsh:TP248.13-248.65, Genotype, Genetics, Pneumocystis jirovecii, Genotyping Techniques, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, 0303 health sciences, biology, Haplotype, biology.organism_classification, Computer Science Applications, Haplotypes, 030220 oncology & carcinogenesis, Microsatellite, Multilocus sequence typing, MultiLocus Sequence Typing, Biotechnology
Abstract: International audience; Pneumocystis jirovecii is an atypical fungus responsible for severe respiratory infections, often reported as local outbreaks in immunocompromised patients. Epidemiology of this infection, and transmission risk emphasises the need for developing genotyping techniques. Currently, two methods have emerged: Multilocus Sequence typing (MLST) and microsatellite length polymorphism (MLP). Here we compare an MLST strategy, including 2 nuclear loci and 2 mitochondrial loci, with an MLP strategy including 6 nuclear markers using 37 clinical PCR-positive respiratory samples from two French hospitals. Pneumocystis jirovecii MLST and MLP provided 30 and 35 different genotypes respectively. A higher number of mixed infections was detected using MLP (48.6% vs. 13.5% respectively; p = 0.002). Only one MLP marker (STR279) was statistically associated with the geographical origin of samples. Haplotype network inferred using the available genotypes yielded expanded network for MLP, characterized by more mutational steps as compared to MLST, suggesting that the MLP approach is more resolutive to separate genotypes. The correlation between genetic distances calculated based on MLST and MLP was modest with a R2 value = 0.32 (p
Published: 2020

4. The Novodiag® Stool parasites assay, an innovative high-plex technique for fast detection of protozoa, helminths and microsporidia in stool samples: a retrospective and prospective study

Author: Sophie Hartuis, Rose-Anne Lavergne, Céline Nourrisson, Jaco Verweij, Guillaume Desoubeaux, Florian Lussac-Sorton, Jean-Philippe Lemoine, Estelle Cateau, Fakhri Jeddi, Philippe Poirier, Patrice Le Pape, Florent Morio, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Parasitologie et Mycologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microvida Laboratory for Medical Microbiology and Immunology, Elisabeth-TweeSteden Hospital, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Nantes University Hospital, Sciences, EDP, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hôpital Bretonneau, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and Nantes Université (Nantes Univ)
Subjects: Microscopy, Veterinary (miscellaneous), [SDV]Life Sciences [q-bio], Gastrointestinal parasites, High-plex detection, Novodiag® Stool Parasites, Comparative evaluation, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Stool, Insect Science, Animal Science and Zoology, Parasitology, Prospective study, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: Objectives: We provide the first evaluation of the CE-IVD marked Novodiag® stool parasites assay (NVD), allowing rapid and high-plex detection of 26 distinct targets, encompassing protozoans, helminths and microsporidia in stool samples. Methods: A total of 254 samples (n = 205 patients) were prospectively processed by the NVD and our routine procedure (RP). Performances of the NVD were compared with RP. Samples only positive by the NVD assay were investigated by external PCR assays. Sensitivity and specificity (Se/Sp) and time from sample receipt to results were determined for each method. The NVD was also evaluated against 77 additional samples positive for a wide range of parasites. Results: Overall positivity rate was 16.9% for RP compared with 34% using the NVD assay, and 164 samples (66%) were negative by both methods. Only 30 positive samples (12%) showed full concordance between RP and NVD. Fifty-three discordant samples were sent for external investigations. Except for Giardia intestinalis and Trichuris spp., higher Se was observed for the NVD assay for Blastocystis spp. (100% vs. 63%), Dientamoeba fragilis (100% vs. 0%), Schistosoma spp. (100% vs. 17%), and Enterobius vermicularis (100% vs. 67%) but roughly similar to RP for the remaining parasites tested. False-positive results were identified for Blastocystis spp., G. intestinalis, and Trichuris spp. using the NVD assay. The NVD mostly provides a diagnosis on the day of sample receipt compared with a mean of three days with RP. Conclusions: Besides some limitations, the NVD is a new diagnostic strategy allowing rapid and high-plex detection of gastrointestinal parasites from unpreserved stools.
Published: 2022

5. Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases

Author: Caroline Denevault-Sabourin, Marc-Antoine Bazin, Isabelle Ourliac-Garnier, Florence O. McCarthy, Marie Brachet-Botineau, Teresinha Gonçalves da Silva, Blandine Baratte, Jérôme Thiéfaine, Viet Hung Dao, Thomas Robert, Stéphane Bach, Cédric Logé, Fabrice Gouilleux, Pascal Marchand, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), University College Cork (UCC), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de criblage d'inhibiteurs de protéines kinases=Kinase Inhibitor Specialized Screening facility (KISSf), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Models, Molecular, Pharmaceutical Science, Organic chemistry, Moths, 01 natural sciences, Analytical Chemistry, CLK1, Docking (dog), QD241-441, hemic and lymphatic diseases, Drug Discovery, Murine leukemia virus, CLK1 kinase, Tumor Cells, Cultured, kinase inhibitors, cercosporamide, chemistry.chemical_classification, 0303 health sciences, Pim kinases, biology, Molecular Structure, Kinase, Protein-Tyrosine Kinases, 3. Good health, Chemistry (miscellaneous), dibenzo[b,d]furan, Molecular Medicine, Cell Survival, Context (language use), Antineoplastic Agents, Protein Serine-Threonine Kinases, Article, 03 medical and health sciences, anticancer agents, Proto-Oncogene Proteins c-pim-1, [CHIM]Chemical Sciences, Animals, Humans, Physical and Theoretical Chemistry, Protein Kinase Inhibitors, 030304 developmental biology, Benzofurans, Cell Proliferation, 010405 organic chemistry, Cell growth, biology.organism_classification, 0104 chemical sciences, Enzyme, chemistry, Cell culture, Cancer research, Drug Screening Assays, Antitumor
Abstract: Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.
Published: 2021

6. In vitro antifungal effect of a plant-based product, CIN-102, on antifungal resistant filamentous fungi and their biofilms

Author: D'Agostino, Maurine, Lemmet, Thomas, Dufay, Claire, Luc, Amandine, Frippiat, Jean Pol, Machouart, Marie, Debourgogne, Anne, Tesse, Nicolas, Lavergne, Rose Anne, Le Pape, Patrice, Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Interactions Gènes-Risques environnementaux et Effets sur la Santé (INGRES), Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Septeos, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: [SDV]Life Sciences [q-bio], female genital diseases and pregnancy complications
Abstract: International audience; Introduction. The increase of invasive fungal infections (IFIs) and associated treatment failure in populations at risk is driving us to look for new treatments. Hypothesis. The CIN-102 compound, derived from cinnamon essential oil, could be a new antifungal class with an activity, in particular, on strains resistant to current antifungals but also on biofilms, a factor of virulence and resistance of fungi. Aim. The aim of this study is to show the activity of CIN-102 on various strains resistant to current antifungals, on the biofilm and to determine the possibility of resistance induced with this compound. Methodology. We studied the MIC of CIN-102 and of current antifungals (voriconazole and amphotericin B) using CLSI techniques against eight different strains of three genera of filamentous fungi involved in IFIs and having resistance phenotypes to current antifungals. We also determined their effects on biofilm formation, and the induced resistance by voriconazole (VRC) and CIN-102. Results. MIC values determined for CIN-102 were between 62.5 and 250 µg ml −1 . We demonstrated the antifungal effect of CIN-102 on biofilm, and more particularly on its formation, with 100 % inhibition achieved for most of the strains. CIN-102 at a sub-inhibitory concentration in the medium did not induce resistance in our strains, even after 30 generations. Conclusions. In this study we show that CIN-102 is effective against resistant filamentous fungi and against biofilm formation. In addition, our strains did not acquire a resistance phenotype against CIN-102 over time, unlike with VRC. CIN-102 is therefore an interesting candidate for the treatment of IFIs, including in cases of therapeutic failure linked to resistance, although further studies on its efficacy, safety and mechanism of action are needed.
Published: 2021

7. Confocal spectral microscopy, a non-destructive approach to follow contamination and biofilm formation of mCherry Staphylococcus aureus on solid surfaces

Author: Munir, Muhammad Tanveer, Munir, Muhammad, Maneewan, Nattar, Pichon, Julien, Gharbia, Mohammed, Oumarou-Mahamane, Ismael, Baude, Jessica, Thorin, Chantal, Lepelletier, Didier, Le Pape, Patrice, Eveillard, Matthieu, Irle, Mark, Pailhoriès, Hélène, Aviat, Florence, Belloncle, Christophe, Federighi, Michel, Dubreil, Laurence, Ecole supérieure du bois (ESB), Ecole supérieure du bois, Laboratoire Innovation Matériau Bois Habitat Apprentissage [Nantes] (LIMBHA), Ecole Supérieure du Bois (ESB), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal Office of Public Health (FOPH - OFSP), Commission Spécialisée Système de santé et sécurité des patients (CS3SP), Haut Conseil de la Santé Publique (HCSP), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), YouR ResearcH-Bio-Scientific [Le Landreau, France], Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National des Sciences Appliquées (INSA), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Sécurité des Aliments (SECALIM), and Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Staphylococcus aureus, Surface Properties, Confocal, Science, 030106 microbiology, medicine.disease_cause, Article, Fluorescence, Applied microbiology, 03 medical and health sciences, Quercus, Microscopy, medicine, [CHIM]Chemical Sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Multidisciplinary, Chromatography, Microscopy, Confocal, biology, Chemistry, Triazines, Spectrum Analysis, Biofilm, Contamination, biology.organism_classification, Wood, Confocal microscopy, Autofluorescence, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Biofilms, Medicine, Quercus petraea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bacterial infection, mCherry
Abstract: Methods to test the safety of wood material for hygienically sensitive places are indirect, destructive and limited to incomplete microbial recovery via swabbing, brushing and elution-based techniques. Therefore, we chose mCherry Staphylococcus aureus as a model bacterium for solid and porous surface contamination. Confocal spectral laser microscope (CSLM) was employed to characterize and use the autofluorescence of Sessile oak (Quercus petraea), Douglas fir (Pseudotsuga menziesii) and poplar (Populus euramericana alba L.) wood discs cut into transversal (RT) and tangential (LT) planes. The red fluorescent area occupied by bacteria was differentiated from that of wood, which represented the bacterial quantification, survival and bio-distribution on surfaces from one hour to one week after inoculation. More bacteria were present near the surface on LT face wood as compared to RT and they persisted throughout the study period. Furthermore, this innovative methodology identified that S. aureus formed a dense biofilm on melamine but not on oak wood in similar inoculation and growth conditions. Conclusively, the endogenous fluorescence of materials and the model bacterium permitted direct quantification of surface contamination by using CSLM and it is a promising tool for hygienic safety evaluation.
Published: 2021

8. A novel and efficient approach to high-throughput production of HLA-E/peptide monomer for T-cell epitope screening

Author: Vaurs, Juliette, Douchin, Gaël, Echasserieau, Klara, Oger, Romain, Jouand, Nicolas, Fortun, Agnès, Hesnard, Leslie, Croyal, Mikaël, Pecorari, Frédéric, Gervois, Nadine, Bernardeau, Karine, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), LabEX IGO Immunothérapie Grand Ouest, Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Nuclear Oncology (CRCINA-ÉQUIPE 13), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Unité de recherche de l'institut du thorax (ITX-lab), and Bernardo, Elizabeth
Subjects: Protein Conformation, Science, Biological techniques, Immunology, Histocompatibility Antigens Class I, Epitopes, T-Lymphocyte, [SDV.CAN]Life Sciences [q-bio]/Cancer, Photochemical Processes, Article, High-Throughput Screening Assays, Major Histocompatibility Complex, [SDV.CAN] Life Sciences [q-bio]/Cancer, Immunologic Techniques, Medicine, Humans, Amino Acid Sequence, Peptides, Biotechnology, Protein Binding, T-Lymphocytes, Cytotoxic
Abstract: International audience; Over the past two decades, there has been a great interest in the study of HLA-E-restricted αβ T cells during bacterial and viral infections, including recently SARS-CoV-2 infection. Phenotyping of these specific HLA-E-restricted T cells requires new tools such as tetramers for rapid cell staining or sorting, as well as for the identification of new peptides capable to bind to the HLA-E pocket. To this aim, we have developed an optimal photosensitive peptide to generate stable HLA-E/pUV complexes allowing high-throughput production of new HLA-E/peptide complexes by peptide exchange. We characterized the UV exchange by ELISA and improved the peptide exchange readout using size exclusion chromatography. This novel approach for complex quantification is indeed very important to perform tetramerization of MHC/peptide complexes with the high quality required for detection of specific T cells. Our approach allows the rapid screening of peptides capable of binding to the non-classical human HLA-E allele, paving the way for the development of new therapeutic approaches based on the detection of HLA-E-restricted T cells.
Published: 2021

9. Characterisation of the antifungal effects of a plant-based compound, CIN-102, on the main septal filamentous fungi involved in human pathology

Author: Maurine D'Agostino, Nicolas Tesse, Rose Anne Lavergne, Patrice Le Pape, Jean Philippe Bouchara, Jean Pol Frippiat, Marie Machouart, Anne Debourgogne, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Septeos, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Antifungal Agents, Terpenes, [SDV]Life Sciences [q-bio], Fungi, Antifungal, Benzoates, Microbiology, QR1-502, Drug Combinations, Aspergillus, Fusarium, Cinnamates, Amphotericin B, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Scedosporium, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; ObjectivesToday, the increase of invasive fungal infections and the emergence of resistant strains are observed in medical practice. New antifungals are expected, and the plant world offers a panel of potentially active molecules. CIN-102 is a mixture of seven different compounds of plant origin developed from the formulation of cinnamon essential oil.MethodsThe in vitro activity of CIN-102 was characterised against Aspergillus spp., Fusarium spp. and Scedosporium spp. by studying the minimum inhibitory concentration (MIC), inoculum effect, germination inhibition, fungal growth, post-antifungal effect (PAFE) and synergy.ResultsMICs determined for the three genera followed a unimodal distribution and their mean values ranged from 62–250 μg/mL. CIN-102 demonstrated an inoculum effect similar to voriconazole and amphotericin B, 100% inhibition of spore germination and a PAFE.ConclusionCIN-102 has significant activity against filamentous fungi involved in human pathologies and should be further explored as a potential new treatment. Other studies regarding its mechanisms of action as well as animal investigations are awaited
Published: 2021

10. New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

Author: Cécile Croix, Pascal Berthelot, Bruno Oyallon, Jean Guillon, Cédric Logé, Stéphane Bach, Marie-Claude Viaud-Massuard, Caroline Denevault-Sabourin, Fabrice Gouilleux, Marie Brachet-Botineau, Thomas Robert, Sajida Ibrahim, William Raoul, Noël Pinaud, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), GICC EA 7501, IMT (Innovation moléculaire et thérapeutique) (IMT), Université de Tours (UT)-Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche de Roscoff (FR2424), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), North-West University [South Aftrica] (NWU), GICC EA 7501, PATCH (Pharmacologie des anticorps thérapeutiques chez l'Homme) (PATCH), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Université de Tours, Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Université de Tours, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), GICC EA 7501, LNOx (Niche leucémique et métabolisme redOx) (LNOx), Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS), IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, INSERM U12132-UMR CNRS 5320, Univ. Bordeaux, ISM, UMR-5255, F-33405 Talence, France, CNRS, ISM, UMR5255, (CNRS, ISM, UMR5255, ), Raoul, William, University of Tours, F-37200 Tours, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU de Lille, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Université de Bordeaux (UB), and Université Bordeaux Segalen - Bordeaux 2
Subjects: Protein Conformation, [SDV]Life Sciences [q-bio], Pharmaceutical Science, Chemistry Techniques, Synthetic, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Analytical Chemistry, Metastasis, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Drug Discovery, Murine leukemia virus, 0303 health sciences, Pim kinases, anticancer targeted therapy, biology, Kinase, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Myeloid leukemia, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Molecular Docking Simulation, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, Molecular Medicine, kinase inhibitor, PIM1, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Protein Serine-Threonine Kinases, Article, lcsh:QD241-441, 03 medical and health sciences, Quinoxaline, Proto-Oncogene Proteins c-pim-1, [SDV.CAN] Life Sciences [q-bio]/Cancer, lcsh:Organic chemistry, Proto-Oncogene Proteins, Quinoxalines, quinoxaline, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Protein Kinase Inhibitors, 030304 developmental biology, Organic Chemistry, Cancer, medicine.disease, biology.organism_classification, In vitro, chemistry, Cancer research
Abstract: International audience; Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.
Published: 2021

11. Ibrutinib, a Bruton's tyrosine kinase inhibitor, a new risk factor for cryptococcosis

Author: B Mahe, M. Leterrier, Thomas Guimard, J. Mahe, David Boutoille, M. Morrier, J. Brochard, F. Morio, P. Le Pape, François Raffi, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Oncology, medicine.medical_specialty, medicine.drug_class, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], Tyrosine-kinase inhibitor, 03 medical and health sciences, chemistry.chemical_compound, Piperidines, Risk Factors, Internal medicine, Pharmacovigilance, medicine, Humans, In patient, Risk factor, Protein Kinase Inhibitors, 0303 health sciences, 030306 microbiology, business.industry, Adenine, Cryptococcosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Infectious Diseases, chemistry, Ibrutinib, business, Bruton's tyrosine kinase inhibitor
Abstract: Purpose Invasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor. Patients and method We reported three additional cases and reviewed 16 previous published cases together with cases from the international pharmacovigilance database. Results Patients were mainly treated for chronic lymphocytic leukemia. Cryptococcosis mostly occurred during the first six months (66%) and especially the first two months (44%) of treatment. Clinical presentation is often pulmonary (68%) and the outcome is usually favorable despite ibrutinib continuation. Conclusion Clinicians must be aware of this infection in patients with hematological malignancies on ibrutinib.
Published: 2020

12. Survival of Bacterial Strains on Wood (Quercus petraea) Compared to Polycarbonate, Aluminum and Stainless Steel

Author: Patrice Le Pape, Laurence Dubreil, Ju-Chi Chen, Muhammad Tanveer Munir, Michel Federighi, Hélène Pailhoriès, Didier Lepelletier, Florence Aviat, Matthieu Eveillard, Christophe Belloncle, Mark Irle, Ecole supérieure du bois (ESB), Ecole supérieure du bois, Your ResearcH Biosc, Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sécurité des Aliments (SECALIM), Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Bactériologie et d'Hygiène Hospitalière, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Laboratoire Innovation Matériau Bois Habitat Apprentissage [Nantes] (LIMBHA), Ecole Supérieure du Bois (ESB), BABARIT, Candice, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Microbiology (medical), Veterinary medicine, [SDV]Life Sciences [q-bio], 030106 microbiology, education, Quercus petraea, healthcare-associated pathogens, Context (language use), [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Biochemistry, Microbiology, hospital environment, Enterococcus faecalis, antimicrobial materials, 03 medical and health sciences, 0302 clinical medicine, medicine, Pharmacology (medical), 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, ComputingMilieux_MISCELLANEOUS, biology, Brief Report, lcsh:RM1-950, sessile oak, Antimicrobial, biology.organism_classification, Acinetobacter baumannii, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [SDV] Life Sciences [q-bio], lcsh:Therapeutics. Pharmacology, Infectious Diseases, Viable count, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Staphylococcus aureus, Bacteria, wood
Abstract: Healthcare-associated infections (HAI) remain a burden in healthcare facilities, environmental surfaces being a potential reservoir for healthcare-associated pathogens. In this context, exploration of materials with potential antimicrobial activities represents a way forward for the future. Here, we explored the survival of four bacterial species commonly involved in HAI (Acinetobacter baumannii, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus), on oak versus three other materials (aluminum, polycarbonate, stainless steel). Twenty microliters of each bacterial suspension (approximatively 107 bacteria) were deposited on each material. Bacterial counts were measured by grinding and culturing on day 0, 1, 2, 6, 7 and 15. Analyses were performed in triplicate for each material and each time evaluated. It appeared that the bacteria viable count decreased rapidly on transversal and tangential oak compared with the other materials for all bacterial species. Furthermore, no difference was noticed between transversal and tangential oak. These results underline the potential for use of oak materials in healthcare facilities, a consideration that should be supported by further investigations.
Published: 2020

13. Wood materials for limiting the bacterial reservoir on surfaces in hospitals: would it be worthwhile to go further?

Author: Didier Lepelletier, Hélène Pailhoriès, Laurence Dubreil, Patrice Le Pape, Christophe Belloncle, Florence Aviat, Matthieu Eveillard, Mark Irle, Muhammad Tanveer Munir, Michel Federighi, Ecole supérieure du bois (ESB), Ecole supérieure du bois, ‎ Your Res Biosci, Université de Nantes (UN), Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sécurité des Aliments (SECALIM), Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire de Bactériologie et d'Hygiène Hospitalière, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire Innovation Matériau Bois Habitat Apprentissage [Nantes] (LIMBHA), Ecole Supérieure du Bois (ESB), BABARIT, Candice, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, Microbiology (medical), Acinetobacter baumannii, Staphylococcus aureus, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, Quercus petraea, Microbial Sensitivity Tests, medicine.disease_cause, Microbiology, hospital environment, 03 medical and health sciences, Quercus, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, 030212 general & internal medicine, Agar diffusion test, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS, Equipment and Supplies, Hospital, Disease Reservoirs, Cross Infection, biology, Pseudomonas aeruginosa, Acinetobacter, Antimicrobial, biology.organism_classification, infection control, Hospitals, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Equipment Contamination, wood
Abstract: International audience; Aim: To assess the activity of Quercus petraea (oak) on five bacterial species/genus frequently involved in hospital-acquired infections for evaluating the interest of going further in exploring the possibilities of using untreated wood as a material in the hospital setting. Materials & methods: We studied the activity of Q. petraea by the disk diffusion method. Results: Q. petraea was active on Staphylococcus aureus and Acinetobacter coalcoaceticus-baumannii complex, two bacterial species particularly resistant in the hospital environment, independently from their resistance to antibiotics, and was slightly active on Pseudomonas aeruginosa. Concurrently, Q. petraea was not active on Enterococci and Escherichia coli. Conclusion: Overall, untreated wood material presented antimicrobial properties that could have an impact on the cross-transmission of certain bacterial species in healthcare settings.
Published: 2020

14. Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols

Author: Guillaume Le Baut, Patrice Le Pape, Marc Le Borgne, Fabrice Pagniez, Sook Wah Yee, Angélique Mularoni, Marie-Pierre Lézé, Mathieu Marchivie, Young Min Na, Patricia Pinson, Isabelle Krimm, Claire Simons, Jean Guillon, Rolf W. Hartmann, Tarek Hakki, Ruben Abagyan, Rita Bernhardt, Nicolas Lebouvier, Da Shi, Institut de sciences exactes et appliquées (ISEA), Université de la Nouvelle-Calédonie (UNC), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Skaggs School of Pharmacy and Pharmaceutical Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Saarland University [Saarbrücken], Cardiff University, Molécules bioactives et chimie médicinale (B2MC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This research was financially supported by Yang Ji Chemical Company of South Korea., Cibles et Médicaments des Infections et de l'Immunité (IICiMed), University of California (UC)-University of California (UC), Le Borgne, Marc, and BUNC, Pole ID
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Pharmaceutical Science, lcsh:Medicine, lcsh:RS1-441, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, Imidazole, cytochromes P450, Candida albicans, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, Absolute configuration, Pharmacology and Pharmaceutical Sciences, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, 5.1 Pharmaceuticals, 030220 oncology & carcinogenesis, docking, Molecular Medicine, antifungal agents, Development of treatments and therapeutic interventions, Stereochemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, azoles, Triazole, CYP51, Article, Vaccine Related, lcsh:Pharmacy and materia medica, 03 medical and health sciences, Candida species, Biodefense, microwave irradiation, X-ray crystallography, Indole test, Aryl, Prevention, lcsh:R, selectivity, biology.organism_classification, 030104 developmental biology, chemistry, indole, Candidaspecies, Azole, Enantiomer
Abstract: A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (&minus, )-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 &micro, g/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 &micro, g/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 &micro, g/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14&alpha, demethylase (CaCYP51). The (&minus, )-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.
Published: 2020
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15. An individual-based model to assess the spatial and individual heterogeneity of Brucella melitensis transmission in Alpine ibex

Author: Sophie Rossi, Pascal Marchand, Bruno Garin-Bastuji, Elodie Petit, Sébastien Lambert, Dominique Gauthier, Emmanuelle Gilot-Fromont, Carole Toïgo, Jean-Michel Gaillard, Anne Thébault, Systèmes de Référence Temps Espace (SYRTE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Biodémographie évolutive, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Office National de la Chasse et de la Faune Sauvage (ONCFS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Direction de l'Evaluation des Risques (DER), This work was performed using the computing facilities of the CC LBBE/PRABI and of the CC IN2P3, and performed within the framework of the LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon, within the program 'Investissements d'Avenir' (ANR- 11-IDEX-0007) operated by the French National Research Agency (ANR). The authors want to thank the scientific experts of the ANSES working groups on brucellosis of Alpine ibex in the Bargy massif, and especially Jean-Pierre Ganière and José-Maria Blasco, who helped for the range values of parameters for the sensitivity analysis. The authors also want to thank the field technicians and researchers, especially Jean Hars, from the French Wildlife and Hunting Agency (ONCFS), who performed monitoring and management of the Alpine ibex population. The authors are also grateful to Elizabeta Vergu and Benoit Durand for their precious insights with the design of the ABC calibration, to Vincent Miele for his help optimising the code of the model, to Christian Willisch for answering questions about Alpine ibex mating tactics and to Clément Calenge for his analyses of the social structure of Alpine ibex in our population. They also thank an anonymous referee for constructive comments on a previous version., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), and Direction de la Stratégie et des Programmes (DSP)
Subjects: 0106 biological sciences, education.field_of_study, Capra ibex, biology, Individual heterogeneity, 010604 marine biology & hydrobiology, Ecological Modeling, Population, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, 3. Good health, Spatial heterogeneity, law.invention, Individual based, Transmission (mechanics), law, Evolutionary biology, Spatial variability, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, education, ComputingMilieux_MISCELLANEOUS, Brucella melitensis
Abstract: Heterogeneity of infectious disease transmission can be generated by individual differences in the frequency of contacts with susceptible individuals, in the ability to transmit the infectious agent or in the duration of infection, and by spatial variation in the distribution, density or movements of hosts. Identifying spatial and individual heterogeneity can help improving management strategies to eradicate or mitigate infectious diseases, by targeting the individuals or areas that are responsible for most transmissions. Individual-based models allow quantifying the respective role of these sources of heterogeneity by integrating potential mechanisms that generate heterogeneity and then by tracking transmissions caused by each infected individual. In this study, we provide an individual-based model of endemic brucellosis Brucella melitensis transmission in the population of Alpine ibex (Capra ibex) of the Bargy massif (France) by taking advantage of detailed information available on ibex population dynamics, behaviour, and habitat use, and on epidemiological surveys. This host-pathogen system is expected to be subject of both individual and spatial heterogeneity. We first estimated the transmission probabilities, hitherto unknown, of the two main transmission routes of the infection (i.e., exposure to infectious births/abortions and venereal transmission). Then, we quantified heterogeneity at both individual and spatial levels. We found that both transmission routes are not negligible to explain the data, and that there is a high amount of heterogeneity of the host-pathogen system at the individual level, with females generating around 90% of the new cases of brucellosis infection. Males transmit infection at a lesser extent but still play a non-negligible role because they move between subpopulations and thereby create opportunities for spreading the infection spatially by venereal transmission. Two particular socio-spatial units are hotspots of transmission, and act as sources of transmission for the other units. These results may have important implications for disease management strategies.
Published: 2020

16. Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives

Author: Laurent Meijer, Nadège Loaëc, Carole Dubouilh-Benard, Marie-Renée Nourrisson, Yvonnick Loidreau, Thierry Besson, Pascal Marchand, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), ManRos Therapeutics, Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Stereochemistry, CK1, CDK5, Pharmaceutical Science, lcsh:Medicine, lcsh:RS1-441, Microwave-assisted chemistry, 01 natural sciences, lcsh:Pharmacy and materia medica, 03 medical and health sciences, chemistry.chemical_compound, Harmine, Protein kinases, Furan, Drug Discovery, Thiophene, [CHIM]Chemical Sciences, 030304 developmental biology, Pyrrole, chemistry.chemical_classification, 0303 health sciences, GSK-3, 010405 organic chemistry, Kinase, Communication, Cyclin-dependent kinase 5, lcsh:R, DYRK1A, 0104 chemical sciences, chemistry, Molecular Medicine, Casein kinase 1, Tricyclic
Abstract: We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1/ε, GSK3 and DYRK1A). As a result, we have identified promising compounds targeting CK1/ε and DYRK1A and displaying micromolar and submicromolar IC50 values.
Published: 2020

17. New azole antifungals with a fused triazinone scaffold

Author: David Montoir, Isabelle Ourliac-Garnier, Aurélien Planchat, Kossi Efouako Soklou, Carine Picot, Rémi Guillon, Sophie Gazzola, Alain Tonnerre, Cédric Logé, Fabrice Pagniez, Patrice Le Pape, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Azoles, Filamentous fungi, 4]triazin-4-one, [SDV]Life Sciences [q-bio], Rhizopus oryzae, Microbial Sensitivity Tests, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 01 natural sciences, Invasive fungal infections, Aspergillus fumigatus, Microbiology, Mice, Structure-Activity Relationship, 03 medical and health sciences, MESH: Animals Antifungal Agents / chemistry Antifungal Agents / pharmacology* Candida albicans / drug effects* Candidiasis / drug therapy* Candidiasis / microbiology Drug Resistance, Fungal Mice Microbial Sensitivity Tests Molecular Structure Structure-Activity Relationship Triazines / chemistry, Drug Resistance, Fungal, Candida albicans, Drug Discovery, medicine, Animals, Antifungal agents, 3H-pyrrolo[1, 030304 developmental biology, Candida, Pharmacology, Voriconazole, chemistry.chemical_classification, 0303 health sciences, 2-d][1, Molecular Structure, biology, Triazines, 010405 organic chemistry, Organic Chemistry, Candidiasis, General Medicine, biology.organism_classification, 0104 chemical sciences, 3. Good health, Enzyme, chemistry, Mucor circinelloides, Azole, Efflux, medicine.drug
Abstract: International audience; We identified a new series of azole antifungal agents bearing a pyrrolotriazinone scaffold. These compounds exhibited a broad in vitro antifungal activity against pathogenic Candida spp. (fluconazole-susceptible and fluconazole-resistant) and were 10- to 100-fold more active than voriconazole against two Candida albicans isolates with known mechanisms of azole resistance (overexpression of efflux pumps and/or specific point substitutions in the Erg11p/CYP51 enzyme). Our lead compound 12 also displayed promising in vitro antifungal activity against some filamentous fungi such as Aspergillus fumigatus and the zygomycetes Rhizopus oryzae and Mucor circinelloides and an in vivo efficiency against two murine models of lethal systemic infections caused by Candida albicans.
Published: 2020

18. Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent

Author: Fabrice Pagniez, Patrice Le Pape, Nicolas Lebouvier, Marc Le Borgne, Carine Picot, Isabelle Ourliac-Garnier, Young Min Na, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut de sciences exactes et appliquées (ISEA), Université de la Nouvelle-Calédonie (UNC), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Molécules bioactives et chimie médicinale (B2MC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Le Borgne, Marc, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Antifungal Agents, Indoles, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Phospholipase, 01 natural sciences, chemistry.chemical_compound, Mice, Ergosterol, Drug Discovery, polycyclic compounds, Cytotoxicity, Candida, ergosterol production, Triazole-indole hybrid, General Medicine, Corpus albicans, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, medicine.drug, Research Paper, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, RM1-950, Microbial Sensitivity Tests, Cell Line, Therapeutic index, Species Specificity, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine, Candida species, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pharmacology, Indole test, 010405 organic chemistry, 1,2,4-Triazole, Triazoles, in vivo evaluation, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Therapeutics. Pharmacology, Fluconazole, phospholipase A2-like activity
Abstract: International audience; (2-(2,4-Dichlorophenyl)-3-(1H-indol-1-yl)-1-(1,2,4-1H-triazol-1-yl)propan-2-ol (8 g), a new 1,2,4-triazole-indole hybrid molecule, showed a broad-spectrum activity against Candida, particularly against low fluconazole-susceptible species. Its activity was higher than fluconazole and similar to voriconazole on C. glabrata (MIC90 = 0.25, 64 and 1 µg/mL, respectively), C. krusei (MIC90 = 0.125, 64 and 0.125 µg/mL, respectively) and C. albicans (MIC90 = 0.5, 8 and 0.25 µg/mL, respectively). The action mechanisms of 8 g were also identified as inhibition of ergosterol biosynthesis and phospholipase A2-like activity. At concentration as low as 4 ng/mL, 8g inhibited ergosterol production by 82% and induced production of 14a-methyl sterols, that is comparable to the results obtained with fluconazole at higher concentration. 8 g demonstrated moderate inhibitory effect on phospholipase A2-like activity being a putative virulence factor. Due to a low MRC5 cytotoxicity, this compound presents a high therapeutic index. These results pointed out that 8 g is a new lead antifungal candidate with potent ergosterol biosynthesis inhibition.
Published: 2020

19. Multivalent Fucosides with Nanomolar Affinity for the Aspergillus fumigatus Lectin FleA Prevent Spore Adhesion to Pneumocytes

Author: David Deniaud, Sébastien G. Gouin, Emilie Gillon, Patrice Le Pape, Aurore Cabanettes, Annabelle Varrot, Victor Lehot, Yoan Brissonnet, Christophe Dussouy, Sami Brument, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Glycoconjugate, animal diseases, 010402 general chemistry, 01 natural sciences, Catalysis, Fucose, Aspergillus fumigatus, Divalent, chemistry.chemical_compound, Lectins, Animals, Aspergillosis, Humans, [CHIM]Chemical Sciences, Chelation, Cell adhesion, chemistry.chemical_classification, biology, 010405 organic chemistry, Organic Chemistry, Lectin, General Chemistry, Spores, Fungal, bacterial infections and mycoses, HEXA, biology.organism_classification, 0104 chemical sciences, chemistry, Biochemistry, Alveolar Epithelial Cells, biology.protein
Abstract: FleA (or AFL), a fucose lectin, was recently identified in the opportunistic mold Aspergillus fumigatus, which causes fatal lung infections in immunocompromised patients. We designed di-, hexa- and octavalent fucosides with various spacer arm lengths to block the hexameric FleA through chelation. Microcalorimetry measurements showed that the ethylene glycol (EG) spacer arm length has a strong influence on the binding affinity of the divalent fucosides. The relationship between the EG length and chelate binding efficiency to FleA was explored according to polymer theory. Hexa- and octavalent compounds based on cyclodextrin and octameric silsesquioxane scaffolds were nanomolar FleA inhibitors, surpassing their monovalent fucose analogue by more than three orders of magnitude. Importantly, some of the fucosides were highly efficient in preventing fungal spore adhesion to bronchoepithelial cells, with half maximal inhibitory concentration values in the micromolar range. We propose that the synergistic antiadhesive effect observed can be ascribed to chelate binding to FleA and to the formation of conidium aggregates, as observed by optical microscopy. These fucosides are promising tools that can be used to better understand the role of FleA in conidia pathogenicity and host defenses against invasive aspergillosis.
Published: 2018

20. Double positive CD4+CD8+ T cells are part of the adaptive immune response against Candida albicans

Author: Marjorie Albassier, Nidia Alvarez-Rueda, Patrice Le Pape, Adel Touahri, Francine Jotereau, Barbara Misme-Aucouturier, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Adult, Male, 0301 basic medicine, CD8 Antigens, T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Inflammation, Adaptive Immunity, Lymphocyte Activation, Immunophenotyping, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Candida albicans, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Cells, Cultured, biology, Candidiasis, General Medicine, Middle Aged, Acquired immune system, biology.organism_classification, 3. Good health, 030104 developmental biology, Cytokine, CD4 Antigens, Host-Pathogen Interactions, Cytokines, Female, Tumor necrosis factor alpha, medicine.symptom, CD8, 030215 immunology
Abstract: Although multiple immune cells participate in the innate and adaptive immune response against Candida albicans, the elucidation of cellular and inflammation kinetics may be a promising strategy to decipher events propitious to infection eradication. We used an in vitro Candida-human leucocyte coculture approach to study the dynamics of rare CD4+CD8+ double positive T lymphocytes (DP T) produced in response to this fungus. Our results highlight the presence of two phenotypically distinct subsets of DP T cells: CD4hiCD8lo and CD4loCD8hi, and that the different ratio of these cells correlates with infection outcome. The ratio of CD4hiCD8lo over CD4loCD8hi by day 6 was significantly higher in controlled infections and decreased when infection persisted due to a significant increase in the proportion of CD4loCD8hi. When infection was controlled, CD4hiCD8lo T cells secreted IFNγ, TNFα, IL-4 and IL-10 cytokines two days after challenge. By day 2, under conditions of persistent infection, CD4hiCD8lo and CD4loCD8hi T cells secreted significant levels of IL-4 and IL-10, respectively, compared to uninfected cultures. Frequency kinetics and original cytokine profiles detailed in this work indicate that DP T cells could participate in the adaptive immune response to C. albicans.
Published: 2019

21. Structure-based design and profiling of novel 17β-HSD14 inhibitors

Author: Madeira Gírio, Patricia Alexandra, Braun, Florian, Bertoletti, Nicole, Möller, Gabriele, Adamski, Jerzy, Frotscher, Martin, Guragossian, Nathalie, Alexandra, Patrícia, Gírio, Madeira, Le Borgne, Marc, Ettouati, Laurent, Falson, Pierre, Müller, Sebastian, Vollmer, Günther, Heine, Andreas, Klebe, Gerhard, Marchais-Oberwinkler, Sandrine, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Philipps Universität Marburg, Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Helmholtz-Zentrum München (HZM), Saarland University [Saarbrücken], Molécules bioactives et chimie médicinale (B2MC), Université de Lyon-Université de Lyon, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Hôpital d'Instruction des Armées du Val de Grâce, Service de Santé des Armées, Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Chair for Molecular Cell Physiology & Endocrinology, Faculty of Biology, Technical University Dresden, Department of Pharmaceutical Chemistry, Institut de biologie et chimie des protéines [Lyon] (IBCP), Institut für Informatik [Berlin], Freie Universität Berlin, and Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Models, Molecular, 0301 basic medicine, 17-Hydroxysteroid Dehydrogenases, Pyridines, Stereochemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dehydrogenase, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Crystallography, X-Ray, 01 natural sciences, Cofactor, Structure-Activity Relationship, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Oxidoreductase, Drug Discovery, Humans, Enzyme Inhibitors, Cytotoxicity, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, 17β-hydroxysteroid Dehydrogenase Type 14, Crystallography, Inhibitors, Structure-based Design, General Medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0104 chemical sciences, 030104 developmental biology, Enzyme, Drug Design, biology.protein, NAD+ kinase, Selectivity, Estrogen receptor alpha
Abstract: International audience; The human enzyme 17b-hydroxysteroid dehydrogenase 14 (17b-HSD14) oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD þ as cofactor. However, the physiological role of the enzyme remains unclear. We recently described the first class of nonsteroidal inhibitors for this enzyme with compound 1 showing a high 17b-HSD14 inhibitory activity. Its crystal structure was used as starting point for a structure-based optimization in this study. The goal was to develop a promising chemical probe to further investigate the enzyme. The newly designed compounds revealed mostly very high inhibition of the enzyme and for seven of them the crystal structures of the corresponding inhibitor-enzyme complexes were resolved. The crystal structures disclosed that a small change in the substitution pattern of the compounds resulted in an alternative binding mode for one inhibitor. The profiling of a set of the most potent inhibitors identified 13 (K i ¼ 9 nM) with a good selectivity profile toward three 17b-HSDs and the estrogen receptor alpha. This inhibitor displayed no cytotoxicity, good solubility, and auspicious predicted bioavailability. Overall, 13 is a highly interesting 17b-HSD14 inhibitor, which might be used as chemical probe for further investigation of the target enzyme.
Published: 2018

22. Anti-protozoal and anti-fungal evaluation of 3,5-disubstituted 1,2-dioxolanes

Author: Pedro Vásquez-Ocmín, Linh Thuy Nguyen, Patrice Le Pape, Alexis Pinet, Sandrine Cojean, Philippe M. Loiseau, Bruno Figadère, Laurent Ferrié, Alexandre Maciuk, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institute of Marine Biochemistry (IMBC), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Antifungal, Plasmodium, Antifungal Agents, medicine.drug_class, Stereochemistry, Clinical Biochemistry, Antiprotozoal Agents, Pharmaceutical Science, Anti fungal, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Microbial Sensitivity Tests, 01 natural sciences, Biochemistry, Structure-Activity Relationship, Parasitic Sensitivity Tests, parasitic diseases, Drug Discovery, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Candida, Leishmania, Aspergillus, Dose-Response Relationship, Drug, Molecular Structure, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Organic Chemistry, Dioxolanes, biology.organism_classification, 0104 chemical sciences, 3. Good health, 010404 medicinal & biomolecular chemistry, Molecular Medicine, Protozoa, Anti protozoal
Abstract: Endoperoxides are a class of compounds, which is well-known for their antimalarial properties, but few reports exist about 3,5-disubstituted 1,2-dioxolanes. After having designed a new synthetic route for the preparation of these substances, they were evaluated against 4 different agents of infectious diseases, protozoa (Plasmodium and Leishmania) and Fungi (Candida and Aspergillus). Whereas moderate antifungal activity was found for our products, potent antimalarial and antileishmanial activities were observed for a few compounds. The nature of the substituents linked to the endoperoxide ring seems to play an important role in the bioactivities.
Published: 2021

23. Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey

Author: M. Leterrier, Anne Totet, Céline Damiani, Danièle Maubon, Solène Le Gal, Isabelle Accoceberry, Julie Bonhomme, Pierre Marty, E. Bailly, Ermanno Candolfi, Anne Debourgogne, Laurence Millon, Frédéric Dalle, Anne-Pauline Bellanger, Patrice Le Pape, Denis Pons, Christelle Pomares, Yann Le Meur, Marie Machouard, Marie-Laure Dardé, Laurence Delhaes, Ahmed Abou Bacar, Dominique Toubas, Frédéric Gabriel, Estelle Cateau, Gilles Nevez, Loïc Favennec, Marie-Hélène Rodier, Xavier Iriart, Eric Dannaoui, Laurence Lachaud, Guillaume Desoubeaux, Pierre Flori, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire de Parasitologie et Mycologie (Parasito - Myco - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et de mycologie médicales, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Parasitologie et de Pathologie Tropicale de Strasbourg, Faculté de Médecine de Strasbourg, Université de Strasbourg, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de parasitologie et mycologie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Institut de Parasitologie et de Pathologie Tropicale, UMR-I 01 - AMIENS, Université de Picardie Jules Verne (UPJV), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Bordeaux (UB), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Anofel Cryptosporidium National Network, Institut d'Histoire de la Pensée Classique (IHPC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Microbiologie (CHD de la Roche-Sur-Yon), CHD Vendee (La Roche Sur Yon), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Departments of Medical Parasitology and Mycology, Service de néphrologie, Sagem - SAFRAN Gr., Université de Strasbourg (UNISTRA), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), CHU Limoges, Service de Parasitologie-Mycologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Appareil Digestif Environnement Nutrition (ADEN ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Service de parasitologie et de mycologie, Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Chrono-environnement - CNRS - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), CHU Gabriel Montpied [Clermont-Ferrand], Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut d’Histoire des Représentations et des Idées dans les Modernités (IHRIM), Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Clermont Auvergne (UCA)-Université Jean Monnet [Saint-Étienne] (UJM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Microbiology (medical), medicine.medical_specialty, Genotype, Pneumocystis carinii, Organ transplantation, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, genotypes, Surveys and Questionnaires, Internal medicine, Humans, Medicine, Pneumocystis jirovecii, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Genotyping, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Retrospective Studies, Transplant recipients, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, 0303 health sciences, biology, 030306 microbiology, business.industry, Pneumocystis, Pneumonia, Pneumocystis, Outbreak, Organ Transplantation, biology.organism_classification, 3. Good health, Transplantation, Infectious Diseases, Renal transplant, France, business, Pneumocystis Infections
Abstract: The burden of nosocomial Pneumocystis infections in transplantation units in France was evaluated through a retrospective survey. Over 12 years, 16 outbreaks occurred, including 13 among renal transplant recipients (RTRs). We performed Pneumocystis jirovecii genotyping in 5 outbreaks, which suggested that specific strains may have been selected by RTRs.
Published: 2019

24. Effects of light and nitrogen availability on photosynthetic efficiency and fatty acid content of three original benthic diatom strains

Author: Cointet, Eva, Wielgosz-collin, Gaëtane, Bougaran, Gael, Rabesaotra, Vony, Gonçalves, Olivier, Méléder, Vona, Mer, molécules et santé EA 2160 (MMS), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN)-Le Mans Université (UM)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Physiologie et biotechnologie des Algues (PBA), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Bioprocédés Appliqués aux Microalgues (GEPEA-BAM), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Université Bretagne Loire (UBL)
Subjects: Pigments, Light, Algae, Ecological Metrics, Nitrogen, Science, Materials Science, Carbohydrates, Plant Science, Biochemistry, Phosphates, Spectroscopy, Fourier Transform Infrared, [CHIM]Chemical Sciences, Animals, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Fluorometry, Seawater, Biomass, Photosynthesis, Materials, ComputingMilieux_MISCELLANEOUS, Diatoms, Ecology, Organic Compounds, Plant Biochemistry, Physics, Electromagnetic Radiation, Fatty Acids, Organic Chemistry, Ecology and Environmental Sciences, Chemical Compounds, Organisms, Biology and Life Sciences, Eukaryota, Plants, Plankton, Lipids, Invertebrates, Culture Media, Photosynthetic Efficiency, Chemistry, Batch Cell Culture Techniques, Physical Sciences, Phytoplankton, Medicine, Biotechnology, Research Article
Abstract: Microalgal biotechnology has gained considerable importance in recent decades. Applications range from simple biomass production for food and animal feed to valuable products for fuel, pharmaceuticals, health, biomolecules and materials relevant to nanotechnology. There are few reports of the exploration of wider microalgae biodiversity in the literature on high value microalgal compounds, however, because it is believed that there is little to be gained in terms of biomass productivity by examining new strains. Still, without diversity, innovation in biotechnology applications is currently limited. Using microalgal diversity is a very promising way to match species and processes for a specific biotechnological application. In this context, three benthic marine diatom strains (Entomoneis paludosa NCC18.2, Nitzschia alexandrina NCC33, and Staurosira sp NCC182) were selected for their lipid production and growth capacities. Using PAM fluorometry and FTIR spectroscopy, this study investigated the impact of nitrogen repletion and depletion as well as light intensity (30, 100, and 400 μmol.photons.m-2.s-1) on their growth, photosynthetic performance and macromolecular content, with the aim of improving the quality of their lipid composition. Results suggest that under high light and nitrogen limitation, the photosynthetic machinery is negatively impacted, leading cells to reduce their growth and accumulate lipids and/or carbohydrates. However, increasing lipid content under stressful conditions does not increase the production of lipids of interest: PUFA, ARA and EPA production decreases. Culture conditions to optimize production of such fatty acids in these three original strains led to a balance between economic and ecophysiological constraints: low light and no nitrogen limitation led to better photosynthetic capacities associated with energy savings, and hence a more profitable approach.
Published: 2019

25. 26th Annual GP2A Medicinal Chemistry Conference & 32nd Journées Franco-Belges de Pharmacochimie

Author: Pascal Marchand, Christophe Rochais, Thomas CAILLY, Thierry BESSON, Patrick Dallemagne, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, drug design, lcsh:R, lcsh:Medicine, lcsh:RS1-441, Pharmaceutical Science, Meeting Report, Medicinal chemistry, 3. Good health, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Political science, medicinal chemistry, chemical tools, Drug Discovery, Molecular Medicine, [CHIM]Chemical Sciences, 030304 developmental biology
Abstract: International audience; As a joint meeting, the 26th Medicinal Chemistry Conference of GP2A and 32nd Journées Franco-Belges de Pharmacochimie took place between 13th and 15th June at Asnelles sur Mer (Normandie, France), providing a unique opportunity for a wide group of European medicinal chemists to engage. Topics included chemical tools for medicinal chemistry, protein-protein interactions, epigenetics, natural product-inspired molecules, computer-aided drug design, and new strategies for the design and development of drugs. Abstracts of invited lectures, proffered young researcher communications, flash communications and posters presented during the meeting are collected in this report.
Published: 2019

26. Assessment of the first commercial multiplex PCR kit (ParaGENIE Crypto-Micro Real-Time PCR) for the detection of Cryptosporidium spp., Enterocytozoon bieneusi, and Encephalitozoon intestinalis from fecal samples

Author: M. Leterrier, Yohann Le Govic, Adrien Laude, Philippe Poirier, Marie Machouart, Patrice Le Pape, Nicolas Argy, Guillaume Desoubeaux, Frédéric Dalle, Jessica Beser, Nathalie Bourgeois, Rose-Anne Lavergne, Florent Morio, Estelle Cateau, Céline Nourrisson, Françoise Botterel, Stéphane Valot, Christelle Pomares, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Bio-Archéologie et d'Ecologie (CBAE), Université Montpellier 2 - Sciences et Techniques (UM2)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Etude des Interactions Hôte-Parasite (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de parasitologie mycologie (CHU de Dijon), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Public Health Agency of Sweden, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Laboratoire de Parasitologie-Mycologie (CHU de Clermont-Ferrand), CHU Gabriel Montpied [Clermont-Ferrand], Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de parasitologie, mycologie, médecine tropicale CHRU Bretonneau, Laboratoire de Parasitologie Mycologie (AP-HP, Hôpital Bichat), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Parasitologie-Mycologie [CHRU Nancy], Vin Aliment Microbiologie et Stress (VAlMiS), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Parasitologie-Mycologie (AP-HP Hôpital Henri Mondor), Hôpital Henri Mondor, Laboratoire de Parasitologie-Mycologie (CHU de Montpellier), Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Microbiologie (CHD de la Roche-Sur-Yon), CHD Vendee (La Roche Sur Yon), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Microbiology (medical), Enterocytozoon bieneusi, [SDV]Life Sciences [q-bio], 030106 microbiology, Cryptosporidium, Microsporidiosis, Cryptosporidium spp, Sensitivity and Specificity, Microbiology, law.invention, Encephalitozoon intestinalis, 03 medical and health sciences, Feces, 0302 clinical medicine, fluids and secretions, law, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Multiplex polymerase chain reaction, parasitic diseases, medicine, CE-IVD, Humans, 030212 general & internal medicine, DNA, Fungal, Polymerase chain reaction, ComputingMilieux_MISCELLANEOUS, Bacteriological Techniques, biology, Encephalitozoon, General Medicine, Multiplex PCR, DNA, Protozoan, Enterocytozoon, biology.organism_classification, medicine.disease, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, Stool, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Reagent Kits, Diagnostic, Multiplex Polymerase Chain Reaction
Abstract: International audience; Cryptosporidium spp. Enterocytozoon bieneusi and Encephalitozoon intestinalis are opportunistic pathogens responsible for gastrointestinal diseases. We evaluated the ParaGENIE Crypto-Micro Real-Time PCR kit (Ademtech, France), the first CE-IVD compliant PCR assay available for these pathogens. This study was conducted blindly against a reference panel of 115 stool specimens including positive samples for Cryptosporidium spp. (n = 48) and E. bieneusi (n = 38) as well as negative or positive samples for other parasites to test for cross-reactivity. An additional set of samples corresponding to 8 rare Cryptosporidium species was also included. Discrepancies were evaluated with external in-house PCR tests. The ParaGENIE Crypto-Micro PCR assay displayed a sensitivity/specificity of 91.7%/100% and 97.3%/98.7% for Cryptosporidium spp. and E. bieneusi, respectively, and was able to detect all 12 Cryptosporidium species of the reference panel, including rare species. This new CE-IVD assay will facilitate the diagnosis of intestinal cryptosporidiosis and microsporidiosis, a major concern in immunocompromised patients and travelers.
Published: 2019

27. Targeting Degradation of EGFR through the Allosteric Site Leads to Cancer Cell Detachment-Promoted Death

Author: Melkon, Iradyan, Nina, Iradyan, Philippe, Hulin, Artur, Hambardzumyan, Aram, Gyulkhandanyan, Rodolphe, Alves de Sousa, Assia, Hessani, Christos, Roussakis, Guillaume, Bollot, Cyril, Bauvais, Vehary, Sakanyan, Maciejak, Olek, National Academy of Sciences of the Republic of Armenia [Yerevan] (NAS RA), Plateforme MicroPicell [Nantes], Université de Nantes (UN), Structure et activité des biomolécules normales et pathologiques (SABNP), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Synsight, and Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed)
Subjects: autophagy, EGFR, [SDV]Life Sciences [q-bio], cytoskeleton, protein degraders, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article, [SDV] Life Sciences [q-bio], targeting chemotherapy, anoikis, receptor tyrosine kinase, cancer, Bim, allosteric site
Abstract: Targeting epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKI) has been widely exploited to disrupt aberrant phosphorylation flux in cancer. However, a bottleneck of potent TKIs is the acquisition of drug resistance mutations, secondary effects, and low ability to attenuate tumor progression. We have developed an alternative means of targeting EGFR that relies on protein degradation through two consecutive routes, ultimately leading to cancer cell detachment-related death. We describe furfuryl derivatives of 4-allyl-5-[2-(4-alkoxyphenyl)-quinolin-4-yl]-4H-1,2,4-triazole-3-thiol that bind to and weakly inhibit EGFR tyrosine phosphorylation and induce strong endocytic degradation of the receptor in cancer cells. The compound-promoted depletion of EGFR resulted in the sequestration of non-phosphorylated Bim, which no longer ensured the integrity of the cytoskeleton machinery, as shown by the detachment of cancer cells from the extracellular matrix (ECM). Of particular note, the longer CH3(CH2)n chains in the terminal moiety of the anti-EGFR molecules confer higher hydrophobicity in the allosteric site located in the immediate vicinity of the catalytic pocket. Small compounds accelerated and enhanced EGFR and associated proteins degradation during EGF and/or glutamine starvation of cultures, thereby demonstrating high potency in killing cancer cells by simultaneously modulating signaling and metabolic pathways. We propose a plausible mechanism of anti-cancer action by small degraders through the allosteric site of EGFR. Our data represent a rational and promising perspective in the treatment of aggressive tumors.
Published: 2019

28. Rapid diagnostic tests relying on antigen detection from stool as an efficient point of care testing strategy for giardiasis and cryptosporidiosis? Evaluation of a new immunochromatographic duplex assay

Author: Jessica Beser, Adrien Laude, Adeline Goudal, Florent Morio, Frédéric Dalle, Guillaume Desoubeaux, Céline Nourrisson, M. Leterrier, Nathalie Bourgeois, Nicolas Argy, Marie Machouart, Françoise Botterel, Estelle Cateau, Patrice Le Pape, Rose-Anne Lavergne, Stéphane Valot, Christelle Pomares, Yohann Le Govic, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Tours, Service de Parasitologie - Mycologie - Médecine Tropicale, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Anofel Cryptosporidium National Network, Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), Université de Bourgogne (UB), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Bactériologie-Virologie-Parasitologie, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Universitaire Carémeau [Nîmes], Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Giardiasis, Point-of-care testing, 030106 microbiology, Molecular Diagnostic Method, Cryptosporidiosis, Cryptosporidium, Antigens, Protozoan, Sensitivity and Specificity, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Feces, 0302 clinical medicine, Antigen, parasitic diseases, Medicine, Animals, Humans, 030212 general & internal medicine, Prospective Studies, Intestinal Diseases, Parasitic, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Alternative methods, Immunoassay, biology, business.industry, Diagnostic Tests, Routine, Giardia, Diagnostic test, General Medicine, Gold standard (test), biology.organism_classification, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Point-of-Care Testing, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Microscopy is the gold standard for the diagnosis of gastrointestinal parasites but is time-consuming and dependent on operator skills. Rapid diagnostic tests represent alternative methods but most evaluations have been conducted on a limited number of samples preventing their implementation in the clinical setting. We evaluated a new CE-IVD marked immunochromatographic assay (Crypto/Giardia K-SeT®, Coris Bioconcept) for the detection of G. intestinalis and Cryptosporidium spp. in 2 phases (retrospective and prospective) on a set of 482 stool samples including rare Cryptosporidium species. Besides G. intestinalis, this test could represent a rapid and reliable alternative to the modified Ziehl-Neelsen staining for the diagnosis of cryptosporidiosis (sensitivity/specificity were 89.2%/99.3% and 86.7%/100% for G. intestinalis and Cryptosporidium resp.), reducing diagnostic delays. Such strategy would also be time-saving by avoiding wet mount microscopy and concentrations steps, being particularly appropriate for laboratories having little expertise in microscopy or not able to implement molecular diagnostic methods.
Published: 2019

29. Gene flow contributes to diversification of the major fungal pathogen $Candida\ albicans$

Author: Marie-Elisabeth Bougnoux, Gavin Sherlock, Patrick Wincker, Marina Marcet-Houben, Emmanuelle Permal, Toni Gabaldón, Dorothée Diogo, Christophe Battail, Natacha Sertour, Patrice Le Pape, Laurence Ma, Jong Hee Shin, Andrew M. Borman, Julie Poulain, Robin C. May, Jeanne Ropars, Soo Hyun Kim, Christiane Bouchier, Kevin Mosca, Shangrong Fan, Christophe d'Enfert, Corinne Maufrais, Kerstin Voelz, Orazio Romeo, Guillaume Laval, Anuradha Chowdhary, Aurélie Perin, Katja Schwartz, Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona], Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Génétique Evolutive Humaine - Human Evolutionary Genetics, Génomique (Plate-Forme), Institut Pasteur [Paris], Centre de Recherche et Innovation Technologique (CITECH), Stanford University [Stanford], University of Birmingham [Birmingham], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Public Health England [London], University of Delhi, Peking University [Beijing], Chonnam National University [Gwangju], Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), University of Messina, Centro Neurolesi Bonino Pulejo Messina (IRCCS Messina), Centro de Regulación Genómica (CRG), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], the Genoscope (projet #15 AP2008/2009 SNP C. albicans) and the Swiss National Science Foundation (Sinergia CRSII5_173863/1) to C.E., J.R. was supported by a Pasteur-Roux fellowship from Institut Pasteur. D.D. was the recipient of a PhD fellowship from Institut National de la Recherche Agronomique. E.P. was the recipient of a post-doctoral fellowship from the Wellcome Trust (WT088858MA). M.M.-H. and T.G. were supported by a grant from the Spanish Ministry of Economy and Competitiveness, BFU2015–67107 cofunded by the European Regional Development Fund (ERDF). C.E., M.-E.B., S.H.K., and J.H.S. were supported by a grant from the French and Korean Ministries for Foreign Affairs (PHC STAR 2011 25841YA). R.C.M. was supported by project MitoFun, funded by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement No. 614562 and by a Wolfson Research Merit Award from the Royal Society. R.C.M. and K.V. were funded by the Surgical Reconstruction and Microbiology Research Centre, which is supported by the National Institute of Health Research, UK. G.S. was supported by the NIH grants R01-HG003468 and RO1-DE015873. C.E. and T.G. are members of the CNRS GDRI 0814 iGenolevures consortium. High-throughput sequencing has been performed on the Genomics Platform, member of France Génomique consortium (ANR10-INBS-09-08)., We thank Bernard Dujon and Tatiana Giraud for providing insights on an earlier version of this manuscript., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 614562,EC:FP7:ERC,ERC-2013-CoG,MITOFUN(2014), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona] (UPF), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Stanford University, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Gene Flow, Lineage (genetic), Population genetics, Science, [SDV]Life Sciences [q-bio], Genes, Fungal, education, General Physics and Astronomy, Virulence, Loss of Heterozygosity, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Linkage Disequilibrium, Gene flow, 03 medical and health sciences, Gene Frequency, Species Specificity, Candida albicans, Humans, lcsh:Science, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Genetics, Genetic diversity, Multidisciplinary, biology, Whole Genome Sequencing, Candidiasis, Genetic Variation, General Chemistry, biology.organism_classification, Corpus albicans, 3. Good health, 030104 developmental biology, GENERATION SEQUENCING DATA, VULVO-VAGINAL CANDIDIASIS, PARASEXUAL CYCLE, MOLECULAR PHYLOGENETICS, CLINICAL STRAINS, DUBLINIENSIS, AFRICANA, REVEALS, YEAST, DNA, Microbial genetics, lcsh:Q, Pathogens
Abstract: Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify., The fungal pathogen Candida albicans can undergo a parasexual process that may contribute to genetic diversity, but its actual relevance is unclear. Here, Ropars et al. analyse the genomic sequences of 182 C. albicans isolates collected worldwide and find evidence of gene flow and thus parasexuality in nature.
Published: 2018

30. Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90

Author: Alain Tonnerre, Marc-Antoine Bazin, Sophie Barillé-Nion, Muriel Duflos, Philippe Juin, David Montoir, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, and Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed)
Subjects: 0301 basic medicine, Cell cycle progression, Antineoplastic Agents, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, 01 natural sciences, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Breast cancer cell line, Western blot, Cell Line, Tumor, Drug Discovery, medicine, Humans, HSP90 Heat-Shock Proteins, Molecular Targeted Therapy, Amines, Naphthyridines, Novobiocin, Cell Proliferation, Pharmacology, biology, medicine.diagnostic_test, 010405 organic chemistry, Chemistry, Drug discovery, Cell Cycle, Organic Chemistry, General Medicine, Hsp90, 0104 chemical sciences, 3. Good health, 030104 developmental biology, Biochemistry, Drug Design, Chaperone (protein), biology.protein, Hydrophobic and Hydrophilic Interactions, medicine.drug
Abstract: International audience; Hsp90 is an ATP-dependent chaperone known to be overexpressed in many cancers. This way, Hsp90 is an important target for drug discovery. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties, leading to the development of new and more active compounds. Consequently, a new set of novobiocin analogs derived from 1,6-naphthyridin-2(1H)-one scaffold was designed, synthesized and evaluated against two breast cancer cell lines. Subsequently, cell cycle progression and apoptosis were conducted on best candidates, finally Western Blot analysis was performed to measure their ability to induce degradation of Hsp90 client proteins.
Published: 2016

31. Chemoselective access to substituted butenolides via a radical cyclization pathway: mechanistic study, limits and application

Author: Jean-Christophe Rouaud, Carole F. Despiau, Anne Boussonnière, Jacques Lebreton, Fabrice Dénès, Romain Bénéteau, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 010405 organic chemistry, Chemistry, General Chemical Engineering, [CHIM]Chemical Sciences, General Chemistry, 010402 general chemistry, 01 natural sciences, Radical cyclization, Combinatorial chemistry, 0104 chemical sciences
Abstract: We developed a new approach to γ-lactols and methylene-γ-lactols based upon the radical cyclization of aluminium acetals obtained by reduction of α-bromoesters with DIBAL-H. The cyclic aluminium acetals resulting from the cyclization process could engage in situ in further functionalization, as illustrated by the Oppenauer-type oxidation to give the corresponding lactones and γ-butenolides. The preparation of butenolides using this strategy compared favourably with the direct, tin-mediated cyclization of α-bromoesters, for which side reactions such as epimerization via [1,5]-HAT processes have been observed.
Published: 2016

32. Determination of antifungal caspofungin in RPMI-1640 cell culture medium by column-switching HPLC-FLD

Author: Karen Gaudin, Oskar González, Rosa M. Alonso, Beatriz Uribe, Isabelle Ourliac-Garnier, Boubakar B. Ba, P. Le Pape, Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Detection limit, 0303 health sciences, Accuracy and precision, Antifungal Agents, Chromatography, 030306 microbiology, Clinical Biochemistry, Extraction (chemistry), Aqueous two-phase system, Pharmaceutical Science, High-performance liquid chromatography, Culture Media, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Caspofungin, Cell culture, Phase (matter), Drug Discovery, [CHIM]Chemical Sciences, Chromatography, High Pressure Liquid, Spectroscopy, 030304 developmental biology
Abstract: The actual scenario in the fight against fungal infections forces researchers to carry through with resistance studies to improve the therapies. These studies, which are performed in cell culture media, need accurate and sensitive analytical methodologies. That is why, in this work, an analytical method for caspofungin (CSF) concentration determination in RPMI-1640 cell culture medium with on-line sample treatment was developed and validated. CSF concentration was determined by HPLC-FLD using a column-switching procedure. The chromatographic analysis was carried out in less than 10 min using a C8 column (4 × 4 mm, 5 μm) as extraction stationary phase and a HSS T3 column (4.6 × 100 mm, 5 μm) as the analytical column. The used mobile phases were mixtures of phase A: pH 2 (adjusted with TFA) aqueous phase and phase B: ACN. For the extraction, the composition was (95:5, A:B v/v) and for the analysis (60:40, A:B v/v), both done in isocratic elution mode. These chromatographic conditions allowed reaching a limit of quantification of 10 μg/L, using 100 μL of sample with an injected volume of 40 μL. The proposed method was successfully validated in terms of selectivity, carryover, linear concentration range, accuracy and precision according to the criteria established by the Food and Drug Administration. Available amount of CSF in RPMI-1640 solution was found critical. CSF concentrations remained stable up to 2 h at room temperature. The developed method was applied for the direct analysis of CSF concentrations from in vitro experiments in presence of C. glabrata (CAGL18). The results highlight the decrease of cell proliferation even if the CSF amount decreases too, which asks question about the real value of the efficient concentration for CSF antifungal activity.
Published: 2020

33. Evaluation of a new multiplex PCR assay (ParaGENIE G-Amoeba Real-Time PCR kit) targeting Giardia intestinalis, Entamoeba histolytica and Entamoeba dispar/Entamoeba moshkovskii from stool specimens: evidence for the limited performances of microscopy-based approach for amoeba species identification

Author: Estelle Cateau, Nathalie Bourgeois, Marie Machouart, Florent Morio, Fakhri Jeddi, M. Gaboyard, Françoise Botterel, Stéphane Valot, Céline Nourrisson, Frédéric Dalle, Christelle Pomares, P. Le Pape, Adrien Laude, Guillaume Desoubeaux, Y. Le Govic, M. Leterrier, Nicolas Argy, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'économie d'Orleans [2008-2011] (LEO), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Service des Recherches Métallurgiques Appliquées (SRMA), Département des Matériaux pour le Nucléaire (DMN), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de pharmacologie clinique et vigilances, Centre régional, de pharmacovigilance et de renseignement sur les médicaments, Hopital de la Milétrie, Poitiers, Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie (CHU de Poitiers), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Bactériologie-Hygiène, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1 (UB)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Laboratoire d'économie d'Orleans (LEO), Université de Tours, L’UNAM Université, Groupe d’Etude des Interactions Hôte-Pathogène, UPRES EA 3142, CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction de l'Energie Nucléaire (CEA-DEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Statistique, Analyse et Modélisation Multidisciplinaire (SAmos-Marin Mersenne) (SAMM), Université Panthéon-Sorbonne (UP1), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Géosciences Paris Sud (GEOPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Dijon, Biologie–Pharmacie, Pharmacie Centrale [CHU Nantes] (Pôle hospitalo-universitaire PHU7 - BPPC), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision (LAMSADE), Université Paris Dauphine-PSL-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Ademtech S.A., and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA)
Subjects: Giardiasis, 0301 basic medicine, diagnosis, Entamoeba, Feces, Entamoeba dispar/Entamoeba moshkovskii, Giardia intestinalis, 0302 clinical medicine, fluids and secretions, Entamoeba moshkovskii, samples, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Amoeba species, Microscopy, parasitic infections, Entamoebiasis, biology, Entamoeba histolytica, General Medicine, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Real-time polymerase chain reaction, Stool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, antigen-detection, Microbiology (medical), food.ingredient, 030231 tropical medicine, 030106 microbiology, Real-Time Polymerase Chain Reaction, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, Amoeba (genus), 03 medical and health sciences, food, Species Specificity, Multiplex polymerase chain reaction, parasitic diseases, Humans, spp, dispar, Multiplex PCR, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial adhesin, amebiasis, Giardia lamblia, Multiplex Polymerase Chain Reaction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectives Besides the potential to identify a wide variety of gastrointestinal parasites, microscopy remains the reference standard in clinical microbiology for amoeba species identification and, especially when coupled with adhesin detection, to discriminate the pathogenic Entamoeba histolytica from its sister but non-pathogenic species Entamoeba dispar / Entamoeba moshkovskii . However, this approach is time-consuming, requires a high-level of expertise that can be jeopardized considering the low prevalence of gastrointestinal parasites in non-endemic countries. Here, we evaluated the CE-IVD-marked multiplex PCR (ParaGENIE G-Amoeba, Ademtech) targeting E. histolytica and E. dispar / E. moshkovskii and Giardia intestinalis . Methods This evaluation was performed blindly on a reference panel of 172 clinical stool samples collected prospectively from 12 laboratories and analysed using a standardized protocol relying on microscopy (and adhesin detection by ELISA for the detection of E. histolytica ) including G. intestinalis ( n = 37), various amoeba species ( n = 55) including E. dispar ( n = 15), E. histolytica ( n = 5), as well as 17 other gastrointestinal parasites ( n = 80), and negative samples ( n = 37). Results This new multiplex PCR assay offers fast and reliable results with appropriate sensitivity and specificity for the detection of G. intestinalis and E. dispar / E. moshkovskii from stools (89.7%/96.9% and 95%/100%, respectively). Detection rate and specificity were greatly improved by the PCR assay, highlighting several samples misidentified by microscopy, including false-negative and false-positive results for both E. dispar/E. moshkovskii and E. histolytica . Conclusion Given the clinical relevance of amoeba species identification, microbiologists should be aware of the limitations of using an algorithm relying on microscopy coupled with adhesin detection by ELISA.
Published: 2018

34. Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls

Author: Guillaume Le Baut, Claire O'Brien, Paul Pavli, Maryline Roy, Philippe Seksik, Xavier Tréton, Stéphane Nancey, Nicolas Barnich, Madeleine Bezault, Claire Auzolle, Dominique Cazals-Hatem, Jérome Viala, Matthieu Allez, The REMIND GROUP, Jean-Pierre Hugot, Anne Dumay, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Australian National University (ANU), CRI UMR 1149, Lab Excellence Inflamex, Université Paris Diderot - Paris 7 (UPD7), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie, Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), INSERM, U1160, Département de Gastroentérologie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Origine, structure et évolution de la biodiversité, Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Origine, structure et évolution de la biodiversité (OSEB), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Investissements d'Avenir programme, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX ANR-11-IDEX-0005-02, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Microbiology (medical), système immunitaire, Immunology, lcsh:QR1-502, Ileum, Biology, Gut flora, Yersinia, Microbiology, Inflammatory bowel disease, lcsh:Microbiology, yersinia, 03 medical and health sciences, 0302 clinical medicine, NOD2, Immunologie, medicine, mucosal immune system, ATG16L1, innate immunity, Crohn's disease, gut microbiota, ileal mucosa, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, maladie de crohn, medicine.disease, biology.organism_classification, molecular test, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, ileon, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, microflore digestive, IRGM, 030211 gastroenterology & hepatology
Abstract: International audience; Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored.
Published: 2018

35. Structure-based design of novel quinoxaline-2-carboxylic acids and analogues as Pim-1 inhibitors

Author: Marie-Claude Viaud-Massuard, Pascal Bonnet, Bruno Oyallon, Mohamed Souab, Sandrine Ruchaud, Stéphane Bach, Pascal Berthelot, Marie Brachet-Botineau, Fabrice Gouilleux, Caroline Denevault-Sabourin, Thomas Robert, Cédric Logé, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Phophorylation de protéines et Pathologies Humaines (P3H), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, GICC EA 7501, IMT (Innovation moléculaire et thérapeutique) (IMT), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Institut de Recherche en Santé 2 [Nantes] (IRS2), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Plate-forme de criblage d'inhibiteurs de protéines kinases=Kinase Inhibitor Specialized Screening facility (KISSf), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Université de Tours, Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Gouilleux, Fabrice, Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Université de Tours, and Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Models, Molecular, 0301 basic medicine, Quinoxaline, Cell Survival, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Structure-Activity Relationship, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Proto-Oncogene Proteins c-pim-1, [SDV.CAN] Life Sciences [q-bio]/Cancer, Quinoxalines, Drug Discovery, Tumor Cells, Cultured, medicine, Humans, Structure–activity relationship, [CHIM]Chemical Sciences, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Pharmacology, chemistry.chemical_classification, Kinase inhibitor, Dose-Response Relationship, Drug, Molecular Structure, Chemistry, Kinase, Anticancer targeted therapy, Organic Chemistry, Myeloid leukemia, Pim-1, General Medicine, medicine.disease, 3. Good health, Leukemia, 030104 developmental biology, Enzyme, Biochemistry, Docking (molecular), Drug Design, 030220 oncology & carcinogenesis, Lead compound
Abstract: International audience; We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies.
Published: 2018

36. PCR-based detection of Aspergillus fumigatus and absence of azole resistance due to TR 34 /L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis

Author: Florent Morio, Tamic Erwan, Olivier Malard, Taieb Chouaki, Claire Cottrel, Rose-Anne Lavergne, Cyril Page, Xavier Dufour, Patrice Le Pape, Estelle Cateau, Pierre Bonfils, Eric Dannaoui, Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de Parasitologie-Mycologie [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Amiens-Picardie, Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de neurophysique, physiologie, pathologie (UMR 8119), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cognition and Action Group (COGNAC-G - UMR 8257), École normale supérieure - Cachan (ENS Cachan)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Aspergillus, biology, Aspergillus fumigatus, 030106 microbiology, Pcr assay, Azole resistance, Clinical settings, Dermatology, General Medicine, biology.organism_classification, fungal rhinosinusitis, 3. Good health, Microbiology, 03 medical and health sciences, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, azole resistance, Cohort, Etiology, PCR-based detection, Fungal hyphae, TR34/L98H
Abstract: SummaryBackground Fungal rhinosinusitis has a worldwide distribution, comprises distinct clinical entities but is mostly due to Aspergillus among which A. fumigatus plays a major role in European countries. Although, there is accumulating evidence for the emergence of environmentally acquired-azole resistance in A. fumigatus (such as TR34/L98H) in various clinical settings, there is few data for patients with fungal rhinosinusitis. Objectives To investigate the prevalence of A. fumigatus azole resistance due to TR34/L98H in a multicenter cohort of patients with fungal rhinosinusitis. Patients/methods 137 patients with fungal rhinosinusitis admitted between 2002 and 2016 at four French medical centers were retrospectively enrolled. Clinical and mycological findings were collected. Aspergillus fumigatus and the TR34/L98H alteration conferring azole resistance were investigated directly from clinical samples using the commercial CE-IVD marked MycoGENIE® Aspergillus fumigatus Real-Time PCR assay. Results/Conclusions Fungal ball was the more frequent clinical form (n=118). Despite the presence of fungal hyphae at direct microscopic examination, mycological cultures remained negative for 83 out of the 137 patients (60.6%). The PCR assay proved to be useful allowing the identification of A. fumigatus and etiological diagnosis in 106 patients (77.4%) compared with 44 patients (32.1%) when using culture as the reference method. Importantly, neither TR34 nor L98H alterations were evidenced. This article is protected by copyright. All rights reserved.
Published: 2018

37. Development of new highly potent imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1

Author: Françoise Debierre-Grockiego, Espérance Moine, Cédric Logé, Alain Gueiffier, Isabelle Dimier-Poisson, Caroline Denevault-Sabourin, Stéphane Bach, Cécile Enguehard-Gueiffier, Sandrine Ruchaud, Mélanie Pénichon, Nathalie Moiré, Claire Delehouzé, Béatrice Foll-Josselin, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), U1069 N2C, Institut National de la Santé et de la Recherche Médicale (INSERM), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Synthèse et isolement de molécules bio-actives EA 7502 (SIMBA), Université de Tours (UT), Phophorylation de protéines et Pathologies Humaines (P3H), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut für Virologie, Philipps University, Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Région Centre - Fédération de recherche en infectiologie (FéRI) de la région Centre, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Infectiologie Animale et Santé Publique - IASP (Nouzilly, France), Institut National de la Recherche Agronomique (INRA), Université de Tours, UR Infectiologie animale et Santé publique (UR IASP), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Swine, Antiprotozoal Agents, Toxoplasma gondii, chemistry.chemical_element, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Calcium, Anti-apicomplexan, 01 natural sciences, Structure-Activity Relationship, 03 medical and health sciences, Drug Discovery, Animals, Humans, Structure–activity relationship, Protein Kinase Inhibitors, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, Dose-Response Relationship, Drug, Molecular Structure, biology, 010405 organic chemistry, Kinase, Cyclin-dependent kinase 5, Organic Chemistry, Imidazo[1,2-b]pyridazine, General Medicine, biology.organism_classification, Toxoplasma gondii calcium-dependent protein kinase 1, 3. Good health, 0104 chemical sciences, Pyridazines, Enzyme, chemistry, Biochemistry, Docking (molecular), Drug Design, Casein kinase 1, Protein Kinases, Toxoplasma
Abstract: International audience; Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.
Published: 2015

38. New CeO 2 nanoparticles-based topical formulations for the skin protection against organophosphates

Author: Thierry Devers, Tifenn Boutard, Denis Josse, Cécile Bignon, Frédéric Guittard, Arnaud Zenerino, Sonia Amigoni, Surfaces & Interfaces, Laboratoire de physique de la matière condensée (LPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), IUT de Chartres, and Université d'Orléans (UO)
Subjects: inorganic chemicals, Health, Toxicology and Mutagenesis, Nanoparticle, Nanotechnology, engineering.material, Toxicology, Article, Topical skin protection, Paraoxon, Adsorption, Coating, lcsh:RA1190-1270, Skin equivalent, health care economics and organizations, lcsh:Toxicology. Poisons, chemistry.chemical_classification, technology, industry, and agriculture, [CHIM.MATE]Chemical Sciences/Material chemistry, Polymer, Penetration (firestop), Permeation, chemistry, Chemical engineering, Cerium dioxide, Emulsion, engineering, Nanoparticles, Thickening polymers
Abstract: International audience; To reinforce skin protection against organophosphates (OPs), the development of new topical skin protectants (TSP) has received a great interest. Nanoparticles like cerium dioxide (CeO2) known to adsorb and neutralize OPs are interesting candidates for TSP. However, NPs are difficult to disperse into formulations and they are suspected of toxicological issues. Thus we want to study: (1) the effect of the addition of CeO2 NPs in formulations for the skin protection (2) the impact of the doping of CeO2 NPs by calcium; (3) the effect of two methods of dispersion of CeO2 NPs: an O/W emulsion or a suspension of a fluorinated thickening polymer (HASE-F) grafted with these NPs. As a screening approach we used silicone membranes as a skin equivalent and Franz diffusion cells for permeation tests. The addition of purum CeO2 NPs in both formulations permits the penetration to decrease by a 3 to 4-fold factor. The O/W emulsion is the best approach to obtain a film-forming coating with a good reproducibility of the penetration results; whereas the grafting of NPs to a thickener is the best way to obtain an efficient homogenous suspension of CeO2 NPs with a decreased of toxicological impact but the coating is less film-forming which slightly impacts the reproducibility of the penetration results.
Published: 2015

39. Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

Author: Eric Viscogliosi, Maiken Cavling Arendrup, O. Le Rouzic, Boualem Sendid, Saad Nseir, P. Le Pape, Philippe Gosset, N. Bautin, Gabriel Reboux, C. Dauchy, S. Fry, René Wintjens, Emilie Fréalle, Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique de pneumologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université libre de Bruxelles (ULB), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Statens Serum Institut [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Copenhagen = Københavns Universitet (KU), Acting for a healthier population, the Région Hauts- de- France funded this work (Environment Health program, grant no. 2010- 12266 & 2010- 12268), which was also supported by GILEAD Sciences, MSD, and Pfizer grants., This work is dedicated to the memory of Eduardo Dei‐Cas, who actively contributed to the initial design and practical achievement of the FungiCOPD project. We also would like to thank Stéphanie Delvart, Sandrine Bonaventure, Dorothée Monvillers, Michèle Wauquier, Filoména Naji, and Nausicaa Gantois for technical assistance, Dr Isabelle Durand‐Joly, Pr El Moukhtar Aliouat, and Dr Annie Standaert‐Vitse for their steady interest in the work and for fruitful discussions, and all the physicians who participated to the recruitment of patients. This work was partially presented as an oral communication at the 'European Congress of Clinical Microbiology and Infectious Diseases' in 2014, at the congress of the 'French Medical Mycology Society' in 2016, and as a poster at the TIMM‐7 in 2015. RW is a Research Associate at the National Fund for Scientific Research FNRS‐FRS (Belgium)., Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), and University of Copenhagen = Københavns Universitet (UCPH)
Subjects: Drug Resistance, Fungal -- genetics, 0301 basic medicine, Azoles, Male, Antifungal Agents, Exacerbation, MESH: Fungal Proteins/isolation & purification, [SDV]Life Sciences [q-bio], Colony Count, Microbial, Aspergillus fumigatus, MESH: Aspergillus fumigatus/drug effects, MESH: Cytochrome P-450 Enzyme System/drug effects, MESH: Genotype, Pulmonary Disease, Chronic Obstructive, dwelling, Cytochrome P-450 Enzyme System, Genotype, Pulmonary Disease, Chronic Obstructive -- microbiology, Prevalence, Prospective Studies, chemistry.chemical_classification, MESH: Aged, COPD, Azole-resistance, MESH: Middle Aged, biology, MESH: Drug Resistance, Fungal/genetics, Mold environmental exposure, Sciences bio-médicales et agricoles, Middle Aged, 3. Good health, MESH: Pulmonary Disease, Chronic Obstructive/microbiology, MESH: Housing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Air Pollution, Indoor, Acute Disease, Disease Progression, MESH: Acute Disease, MESH: Cytochrome P-450 Enzyme System/isolation & purification, MESH: Disease Progression, Female, medicine.drug, medicine.medical_specialty, Environmental Engineering, Itraconazole, MESH: Fungal Proteins/drug effects, 030106 microbiology, Aspergillus fumigatus -- drug effects -- genetics -- isolation & purification, MESH: Azoles/pharmacology, Fungal Proteins -- drug effects -- isolation & purification, chronic obstructive pulmonary disease, Microbiology, Fungal Proteins, 03 medical and health sciences, azole resistance, MESH: Air Pollution, Indoor/analysis, Drug Resistance, Fungal, Internal medicine, medicine, Humans, MESH: Aspergillus fumigatus/genetics, Dwelling, MESH: Colony Count, Microbial, MESH: Prevalence, Aged, Aspergillus, MESH: Humans, Azoles -- pharmacology, electrostatic dust collector, Public Health, Environmental and Occupational Health, mold environmental exposure, Electrostatic dust collector, Building and Construction, medicine.disease, biology.organism_classification, MESH: Male, MESH: Prospective Studies, chemistry, Cytochrome P-450 Enzyme System -- drug effects -- isolation & purification, Housing, Azole, ARAF, MESH: Aspergillus fumigatus/isolation & purification, Antifungal Agents -- pharmacology, MESH: Antifungal Agents/pharmacology, MESH: Female, Air Pollution, Indoor -- analysis
Abstract: Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34/L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

40. Thermothelomyces thermophila human infections

Author: C. Nourrisson, D. Garcia-Hermoso, F. Morio, C. Kauffmann-Lacroix, N. Berrette, J. Bonhomme, P. Poirier, O. Lortholary, F. Cazenave Roblot, D. Hoinard, E. Launay, R.A. Lavergne, C. Le Naourès Méar, P. Penn, B. Rammaert, K. Sitbon, M. Vidal-Roux, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Université de Clermont-Ferrand, Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), CHU de Nantes, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier du Mans, Centre Hospitalier Le Mans (CH Le Mans), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), French Mycosis Study Group, IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Microbiology (medical), business.industry, 030106 microbiology, Treatment outcome, General Medicine, Microbiological Techniques, Biology, Bioinformatics, biology.organism_classification, 03 medical and health sciences, Infectious Diseases, Text mining, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Sordariales, Molecular diagnostic techniques, Young adult, Thermothelomyces, business, Survival analysis, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience
Published: 2017

41. Crystal structure of N-(7-{[2-(dimethylamino)ethyl]amino}-1-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-3,4,5-trimethoxybenzamide

Author: Guillon, Jean, Montoir, David, Marchivie, Mathieu, Duflos, Muriel, Bazin, Marc-Antoine, Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB)
Subjects: [CHIM.MATE]Chemical Sciences/Material chemistry
Abstract: International audience; The X-ray crystal structure of N-(7-{[2-(dimethylamino)ethyl]amino}-1-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-3,4,5-trimethoxybenzamide, a potential anticancer agent targeting Hsp90, was established. It crystallizes in the triclinic space group P-1 with cell parameters a = 9.3554(4)Å, b = 11.4450(5)Å, c = 11.5629(4)Å, α = 87.140(2), β = 78.8070(19), γ = 69.2119(19), V = 1135.21(8)Å3 and Z = 2. The crystal structure was refined to final values of R1 = 0.0492 and wR2 = 0.1386. An X-ray crystal structure analysis revealed that each molecule features intermolecular N–H···N hydrogen bonds to form dimers.
Published: 2017

42. Antimalarial Activity of Axidjiferosides, New β-Galactosylceramides from the African Sponge Axinyssa djiferi

Author: Fereshteh Farokhi, Monique Clément, Gilles Barnathan, Christos Roussakis, Jean-Michel Kornprobst, Gaëtane Wielgosz-Collin, Emilie Genin-Seward, Philippe M. Loiseau, Philippe Grellier, Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratory of Marine Chemistry, Université de Nantes (UN), Pôle Mer et Littoral, UPRES-EA 2160, Groupe Substances marines à activité biologique Laboratoire de Chimie marine, ISOMer, Nantes, Mer, molécules et santé EA 2160 (MMS), Le Mans Université (UM)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: [SDV]Life Sciences [q-bio], Drug Resistance, Pharmaceutical Science, 01 natural sciences, antimalarial activity, Mice, Neoplasms, Drug Discovery, marine sponge glycolipids, Cytotoxicity, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, 0303 health sciences, biology, glycosphingolipids, Monosaccharides, Chloroquine, Senegal, 3. Good health, Porifera, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Biochemistry, cytotoxicity, Female, Galactosylceramides, Plasmodium falciparum, Ceramides, Article, Axinyssa, 03 medical and health sciences, Antimalarials, Inhibitory Concentration 50, Glycolipid, Cell Line, Tumor, Monosaccharide, Animals, Humans, [CHIM]Chemical Sciences, IC50, 030304 developmental biology, 010405 organic chemistry, biology.organism_classification, In vitro, 0104 chemical sciences, Sponge, chemistry, lcsh:Biology (General)
Abstract: The marine sponge, Axinyssa djiferi, collected on mangrove tree roots in Senegal, was investigated for glycolipids. A mixture containing new glycosphingolipids, named axidjiferoside-A, -B and -C, accounted for 0.07% of sponge biomass (dry weight) and for 2.16% of total lipids. It showed a significant antimalarial activity, with a 50% inhibitory concentration (IC50) of 0.53 ± 0.2 μM against a chloroquine-resistant strain of Plasmodium falciparum. They were identified as homologous β-galactopyranosylceramides composed of 2-amino-(6E)-octadec-6-en-1,3,4-triol, and the major one, axidjiferoside-A (around 60%), contained 2-hydroxytetracosanoic acid. Cytotoxicity was studied in vitro on human cancer cell lines (multiple myeloma, colorectal adenocarcinoma, glioblastoma and two lung cancer NSCLC-N6 and A549). Results of this investigation showed that axidjiferosides are of interest, because they proved a good antiplasmodial activity, with only a low cytotoxicity against various human cell lines and no significant antitrypanosomal and antileishmanial activity. Thus, it seems that galactosylceramides with a β anomeric configuration may be suitable in searching for new antimalarial drugs.
Published: 2013

43. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF)

Author: L. Millon, R. Herbrecht, F. Grenouillet, F. Morio, A. Alanio, V. Letscher-Bru, S. Cassaing, T. Chouaki, C. Kauffmann-Lacroix, P. Poirier, D. Toubas, O. Augereau, S. Rocchi, D. Garcia-Hermoso, S. Bretagne, H. Dupont, J.P. Marolleau, A. Totet, C. Damiani, A. Berceanu, F. Larosa, J. Bonhomme, C. Chabrot, B. Bouteille, D. Boutoille, T. Gastinne, P. Peterlin, M. Gari Toussaint, D. Poisson, D. Briet, J. Buret, M. Legrand, B. Denis, E. Raffoux, A. Bergeron, A. Veinstein, C. Godet, Y. N'guyen, S. Diallo, M. Sabou, J. Denis, M.P. Ledoux, C. Recher, J. Ruiz, G. Desoubeaux, E. Bailly, E. Chachaty, F. Dromer, O. Lortholary, K. Sitbon, D. Hoinard, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service d’Oncologie et d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Saint Louis [APHP], Université Paris Diderot - Paris 7 (UPD7), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Parasitologie-Mycologie [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Picardie Jules Verne (UPJV), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional d'Orléans (CHR), Immunologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de parasitologie et de mycologie médicales, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Istituto di Fisica dello Spazio Interplanetario (INAF), Consiglio Nazionale delle Ricerche [Roma] (CNR), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hématologie Clinique [CHU Hôtel-Dieu, Nantes], Hôtel-Dieu de Nantes, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Association de dépistage des cancers, Mutualité française, Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de physique des interfaces et des couches minces [Palaiseau] (LPICM), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement - Direction Méditerranée (Cerema Direction Méditerranée), Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement (Cerema), UMR1037, Cancer Research Center of Toulouse, Université de Tours, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), service de parasito-mycologie CHU Besancon, service de parasitologie mycologie CHU Jean Minjoz BESANCON, Hôpital Jean Minjoz-Hôpital Jean Minjoz, Université de Nantes ( UN ) - UFR Sciences et Techniques-UFR des Sciences Pharmaceutiques, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Université Paris Diderot - Paris 7 ( UPD7 ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de Parasitologie et de Pathologie Tropicale, Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université de Picardie Jules Verne ( UPJV ), CHU Amiens-Picardie, CHU de Poitiers, CHU Gabriel Montpied ( CHU ), CHU Clermont-Ferrand, Matrice extracellulaire et dynamique cellulaire - UMR 7369 ( MEDyC ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Centre Hospitalier Régional d'Orléans ( CHR ), This work was supported by a grant from French Ministry of Health (Projet Hospitalier de Recherche Clinique, national-ModiMucor 2014-A00580-47). LM has received support for travel to meetings from Pfizer, MSD and Gilead. RH received honorariafrom Astellas, Basilea, Gilead, MSD, Pfizer and Schering-Plough and a research grant from Pfizer. SB received project funding from Renishaw Diagnostics, was sponsored by Pfizer and MSD to attend international meetings, and provided consultancy for Gilead., French Mycosis Study Group, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), CHU Gabriel Montpied [Clermont-Ferrand], Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and CHU Gabriel Montpied (CHU)
Subjects: 0301 basic medicine, Male, Pathology, [SDV]Life Sciences [q-bio], Comorbidity, Quantitative PCR, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diagnosis, Sampling (medicine), 030212 general & internal medicine, DNA, Fungal, Fungemia, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, 80 and over, biology, General Medicine, Middle Aged, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Real-time polymerase chain reaction, Population Surveillance, Mucorales, Female, France, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Internal medicine, medicine, Humans, Mucormycosis, Survival rate, Survival analysis, Aged, Retrospective Studies, [ SDV ] Life Sciences [q-bio], Retrospective cohort study, medicine.disease, biology.organism_classification, Survival Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, monitoring, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p \textless10(-6)). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.
Published: 2016

44. Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France

Author: El Safadi, Dima, Cian, Amandine, Nourrisson, Céline, Pereira, Bruno, Morelle, Christelle, Bastien, Patrick, Bellanger, Anne-Pauline, Botterel, Françoise, Candolfi, Ermanno, Desoubeaux, Guillaume, Lachaud, Laurence, Morio, Florent, Pomares, Christelle, Rabodonirina, Meja, Wawrzyniak, Ivan, Delbac, Frédéric, Gantois, Nausicaa, Certad, Gabriela, Delhaes, Laurence, Poirier, Philippe, Viscogliosi, Eric, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Parasitologie et de Pathologie Tropicale (IPPTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), This work was supported by grants from the Programme Orientations Stratégiques from the University of Lille 2, the Fonds Hospitalier d’Aide à l’Emergence from the CHRU of Lille, the Centre National de la Recherche Scientifique and the Institut Pasteur of Lille. DES was supported by a PhD fellowship from the Conseil National de la Recherche Scientifique and the AZM & Saade Association and AC by a PhD fellowship from the University of Lille 2 and the Institut Pasteur of Lille., Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Gabriel Montpied (CHU), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 (CEPR. Equipe 3), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
Subjects: Adult, Male, Blastocystis sp, Adolescent, Intestinal parasite, Blastocystis Infections, Subtyping, Feces, Young Adult, Risk Factors, Prevalence, Animals, Humans, Child, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Aged, 80 and over, Infant, Middle Aged, Infectious Diseases, PCR, Cross-Sectional Studies, Molecular epidemiology, Child, Preschool, Blastocystis, Risk factors for infection, Female, France, Research Article
Abstract: Background Blastocystis sp. is the most common intestinal parasite of humans. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype distribution of Blastocystis sp. in Europe are rarely reported. Therefore, the first multi-center epidemiological survey performed in Europe was conducted in France to diagnose and subtype Blastocystis sp. and to identify risk factors for infection. Methods Stool samples from 788 patients were collected either in summer or winter in 11 hospitals throughout France together with patient data. All stool samples were tested for the presence of Blastocystis sp. by quantitative PCR targeting the SSU rDNA gene. Positive samples were sequenced to determine the distribution of the subtypes in our cohort. Statistical analyses were performed to identify potential risk factors for infection. Results Using quantitative PCR, the overall prevalence of Blastocystis sp. was shown to reach 18.1 %. The prevalence was significantly higher in summer (23.2 %) than in winter (13.7 %). Travellers or subjects infected with other enteric parasites were significantly more infected by Blastocystis sp. than non-travellers or subjects free of other enteric parasites, respectively. Different age-related epidemiological patterns were also highlighted from our data. The prevalence of Blastocystis sp. was not significantly higher in patients with digestive symptoms or diagnosed with chronic bowel diseases. Among symptomatic patients, Blastocystis sp. infection was significantly associated with abdominal pain. Gender, socioeconomic status, and immune status were not identified as potential risk factors associated with infection. Among a total of 141 subtyped isolates, subtype 3 was predominant (43.3 %), followed by subtype 1 and subtype 4 (20 %), subtype 2 (12.8 %), subtype 6 and subtype 7 (2.1 %). No association between ST and clinical symptoms was statistically evidenced. Conclusions A high prevalence of Blastocystis sp. infection was found in our French patient population. Seasonal impact on the prevalence of Blastocystis sp. was highlighted and recent travels and age were identified as main risk factors for infection. Most cases were caused by subtypes 1 to 4, with a predominance of subtype 3. Large variations in both prevalence and ST distribution between hospitals were also observed, suggesting distinct reservoirs and transmission sources of the parasite. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1776-8) contains supplementary material, which is available to authorized users.
Published: 2016

45. Identification and Biological Activities of Long-Chain Peptaibols Produced by a Marine-Derived Strain of Trichoderma longibrachiatum

Author: Mustapha Mohamed-Benkada, Philippe Vérité, Yves François Pouchus, Nicolas Ruiz, Nathalie Caroff, Fabrice Pagniez, Université des sciences et de la Technologie d'Oran Mohamed Boudiaf [Oran] (USTO MB), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN), Mer, molécules et santé EA 2160 (MMS), Le Mans Université (UM)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Aliments Bioprocédés Toxicologie Environnements (ABTE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), and Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)
Subjects: 0301 basic medicine, Antifungal, food.ingredient, Antifungal Agents, Trichoderma longibrachiatum, medicine.drug_class, Electrospray ionization, [SDV]Life Sciences [q-bio], Bioengineering, Microbial Sensitivity Tests, 01 natural sciences, Biochemistry, Marine-derived fungi, Microbiology, 03 medical and health sciences, food, Cell Line, Tumor, medicine, A-II-a, Agar, Animals, [CHIM]Chemical Sciences, Molecular Biology, Cell Proliferation, Peptaibols, Trichoderma, Biological Products, Chromatography, Strain (chemistry), Bacteria, Longibrachins A-0, 010405 organic chemistry, Chemistry, Diptera, Fungi, General Chemistry, General Medicine, Trichoderma spp, Long-chain peptaibols, Antineoplastic Agents, Phytogenic, Acute toxicity, 0104 chemical sciences, Anti-Bacterial Agents, 030104 developmental biology, Molecular Medicine, Drug Screening Assays, Antitumor, and A-IV-b, Long chain
Abstract: International audience; Six long-chain peptaibols, 1 - 6, were identified from agar cultures of a marine-derived Trichoderma longibrachiatum Rifai strain (MMS151) isolated from blue mussels. The structure elucidation was carried out using electrospray ionization ion trap mass spectrometry (ESI-IT-MS) and GC/EI-MS. The long-chain peptaibols exhibited the general building scheme Ac-Aib-Ala-Aib-Ala-Aib-XXX-Gln-Aib-Vxx-Aib-Gly-XXX-Aib-Pro-Vxx-Aib-XXX-Gln-Gln-Pheol and were similar or identical to recurrent 20-residue peptaibols produced by Trichoderma spp. Three new sequences were identified and were called longibrachins A-0, A-II-a, and A-IV-b. The isolated peptaibols were assayed for cytotoxic, antibacterial, and antifungal activities, and acute toxicity on Dipteran larvae.
Published: 2016

46. Econazole imprinted textiles with antifungal activity

Author: Aicha Benhaddou, Karine Théberge, Martine Raymond, Patrice Le Pape, Augustine Lalloz, Fabrice Pagniez, Mirza Akram Hossain, Jeanne Leblond, Pierre Simard, Université de Montréal (UdeM), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Biomod Concepts Inc., and Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC)
Subjects: Antifungal, Econazole, Antifungal Agents, medicine.drug_class, Swine, Skin Absorption, Pharmaceutical Science, 02 engineering and technology, Administration, Cutaneous, 030226 pharmacology & pharmacy, Microbiology, Molecular Imprinting, 03 medical and health sciences, Mice, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, In vivo, medicine, Animals, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Candida, Skin, Drug Carriers, Chemistry, Textiles, Candidiasis, Temperature, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Lipids, 3. Good health, Drug activity, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Econazole Nitrate, Percutaneous absorption, Female, 0210 nano-technology, Drug carrier, Ex vivo, Biotechnology, medicine.drug, Nuclear chemistry
Abstract: International audience; In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5 ± 0.1 lm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97 ± 3 lg/cm 2) was reproducible and stable up to 4 months storage at 25°C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8°C, which enabled a larger drug release at 32°C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl Ò. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers , where the fungal infections develop, as compared to dermal absorption of Pevaryl Ò. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections.
Published: 2016

47. Amino acid substitutions in the Candida albicans sterol 5,6-desaturase (Erg3p) confer azole resistance: characterization of two novel mutants with impaired virulence

Author: Claire Lacroix, Fabrice Pagniez, Patrice Le Pape, Michel Miegeville, Florent Morio, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Hyphal growth, Antifungal Agents, Drug resistance, Mice, chemistry.chemical_compound, C. albicans, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, Candida albicans, Pharmacology (medical), azole antifungals, Fluconazole, chemistry.chemical_classification, Ergosterol, Virulence, biology, Candidiasis, Middle Aged, amphotericin B, ERG3, Sterols, Infectious Diseases, Female, Oxidoreductases, medicine.drug, Adult, Microbiology (medical), Microbial Sensitivity Tests, ergosterol biosynthesis, Chemoprevention, Gas Chromatography-Mass Spectrometry, Microbiology, Drug Resistance, Fungal, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pharmacology, Gene Expression Profiling, Cell Membrane, Triazoles, biology.organism_classification, Pyrimidines, Amino Acid Substitution, chemistry, Azole, Mutant Proteins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Voriconazole
Abstract: Objectives To determine the mechanisms responsible for fluconazole resistance in two Candida albicans isolates (CAAL2 and CAAL76) recovered from two hospitalized patients after fluconazole prophylaxis. Methods MICs of fluconazole and voriconazole were determined by the broth microdilution method (CLSI M27-A3), and by Etest(®) for amphotericin B. RNA expression levels of CDR1, MDR1 and ERG11 were determined by RT-PCR. Mutations in ERG11 and ERG3 were investigated by amplification and sequencing. Sterol membrane profiles were determined by gas chromatography-mass spectrometry (GC-MS). In vivo virulence was determined in a murine model of invasive candidiasis. Results Both isolates displayed azole cross-resistance and reduced susceptibility to amphotericin B, and are novel Δ(5,6)-desaturase (Erg3p) mutants. CAAL2 harbours a new amino acid substitution (L193R), whereas a 13 bp deletion leading to a truncated Erg3p (Δ366-378) was found in CAAL76. Both genetic alterations impaired Erg3p function as shown by GC-MS in these isolates (ergosterol content below 10%, and accumulation of ergosta-7,22-dienol above 40%). In vivo, in a murine model of invasive candidiasis, both CAAL2 and CAAL76 exhibited a significant trend toward reduced virulence, which seems to be linked to a reduced capacity for hyphal growth. Conclusions These findings demonstrate the critical role of residue 193 in Erg3p function and azole resistance. We suggest that this attenuated in vivo virulence phenotype could be linked to lower potential for hyphal growth. Taken together, our findings highlight the fact that erg3 mutants must be considered in future studies aiming at investigating azole antifungal drug resistance.
Published: 2012

48. Radical Cyclization of α-Bromo Aluminum Acetals onto Alkenes and Alkynes (Radic[Al] Process): A Simple Access to γ-Lactols and 4-Methylene-γ-Lactols

Author: Romain Bénéteau, Anne Boussonnière, Nicolas Zimmermann, Fabrice Dénès, Jacques Lebreton, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 010405 organic chemistry, Organic Chemistry, chemistry.chemical_element, General Chemistry, 010402 general chemistry, 01 natural sciences, Radical cyclization, Catalysis, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Aluminium, Propargyl, [CHIM]Chemical Sciences, Surface modification, Organic chemistry, Methylene
Abstract: An efficient preparation of gamma-lactols and methylene-gamma-lactols is described. Highly acid-sensitive lactols are prepared in a concise manner by using a radical cyclization of aluminum acetals. The precursors for the radical reactions are readily prepared from allyl or propargyl alcohols and alpha-bromo acids. Functionalization of the resulting gamma-lactols and methylene-gamma-lactols can be achieved following isolation, leading to synthetically useful building blocks, such as 1,4-diols, 1,4-dienes, gamma-lactones, and polysubstituted tetrahydrofurans.
Published: 2011

49. Design, synthesis and evaluation of 3-(imidazol- 1-ylmethyl)indoles as antileishmanial agents. Part II

Author: Sophie Barres, Damien Crepin, Carine Picot, Cédric Logé, Patrice Le Pape, Marc Le Borgne, Fabrice Pagniez, Francis Giraud, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Quantitative structure–activity relationship, Indoles, Stereochemistry, Antiparasitic, medicine.drug_class, Leishmania mexicana, Antiprotozoal Agents, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Inhibitory Concentration 50, Structure-Activity Relationship, chemistry.chemical_compound, Drug Discovery, medicine, Animals, Molecule, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS, Biological evaluation, Pharmacology, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Imidazoles, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, Combinatorial chemistry, 0104 chemical sciences, Design synthesis, Drug Design, Benzyl group
Abstract: A new series of 1-benzyl-3-(imidazol-1-ylmethyl)indoles were synthesized according to a previous 3D-QSAR predictive model and assayed for their antiparasitic activity upon Leishmania mexicana promastigotes. The biological results obtained for these twelve molecules showed an IC(50) ranging from 2.3 to 32 microM and mainly illustrated the importance of the hydrophobic parameter the para-position of the benzyl group. In order to improve the activities of these compounds and to check the potential influence of the electronic parameter on this particular position, a Craig diagram was used to select original electro-donating and lipophilic substituents. Synthesis and biological evaluation of ten new compounds (IC(50) between 2.5 and 5.4 microM) confirmed that only the hydrophobic field is essential for a high level of activity.
Published: 2009

50. Novel 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitrile derivatives as dual cyclin-dependent kinase 1 (CDK1)/glycogen synthase kinase-3 (GSK-3) inhibitors: Synthesis, biological evaluation and molecular modeling studies

Author: Alexandra Testard, Cédric Logé, Olivier Lozach, Laurent Meijer, Mélina Blairvacq, Thierry Besson, Jean-Michel Robert, Valérie Thiéry, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Génie Protéique et Cellulaire (LGPC), Université de La Rochelle (ULR), Station biologique de Roscoff (SBR), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Magnetic Resonance Spectroscopy, Spectrophotometry, Infrared, Stereochemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, Chemical synthesis, Amidine, Glycogen Synthase Kinase 3, 03 medical and health sciences, chemistry.chemical_compound, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Cyclin-dependent kinase, GSK-3, CDC2 Protein Kinase, Nitriles, Drug Discovery, Quinazoline, Enzyme Inhibitors, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Cyclin-dependent kinase 1, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Organic Chemistry, [CHIM.CATA]Chemical Sciences/Catalysis, General Medicine, 3. Good health, 0104 chemical sciences, Biochemistry, Quinazolines, biology.protein, Tau-protein kinase
Abstract: Continuous efforts in microwave-assisted synthesis and the structure-activity relationships' (SARs) studies of novel modified 9-oxo-thiazolo[5,4-f]quinazoline-2-carbonitriles, allowed identification of new amidine and imidate derivatives as potent and dual CDK1/GSK-3 inhibitors. Combination of lead optimization and molecular modeling studies allowed identification of a dual CDK1/GSK-3 inhibitor (compound 13d) with submicromolar values.
Published: 2008

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