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1. Population Analysis of Escherichia coli Sequence Type 361 and Reduced Cefiderocol Susceptibility, France

Author

Jousset, Agnes B., Bouabdallah, Laura, Birer, Aurelien, Rosinski-Chupin, Isabelle, Mariet, Jean-Francois, Oueslati, Saoussen, Emeraud, Cecile, Girlich, Delphine, Glaser, Philippe, Naas, Thierry, Bonnin, Remy A., and Dortet, Laurent

Subjects
Beta lactamases -- Genetic aspects, Protein binding -- Genetic aspects, Imipenem, Infection -- Genetic aspects, Escherichia coli -- Genetic aspects, Health
Abstract

Few last-line antimicrobial agents effectively treat infections caused by New Delhi metallo-[beta]-lactamase (NDM)-producing Enterobacterales (1). Cefiderocol is a novel synthetic conjugate siderophore cephalosporin that is more stable against [beta]-lactamase hydrolysis [...]

Published
2023
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4. Molecular, Genetic, and Biochemical Characterization of OXA-484 Carbapenemase, a Difficult-to-Detect R214G Variant of OXA-181.

Author

Gonzalez, Camille, Oueslati, Saoussen, Rima, Mariam, Nermont, Réva, Dortet, Laurent, Hopkins, Katie L., Iorga, Bogdan I., Bonnin, Rémy A., and Naas, Thierry

Subjects
ESCHERICHIA coli, DRUG resistance in bacteria, CARBAPENEMASE, IMIPENEM, CARBAPENEMS
Abstract

OXA-244, an R214G variant of OXA-48, is silently spreading worldwide likely because of difficulties in detection using classical screening media. Here, we characterized two clinical isolates of Escherichia coli and Citrobacter youngae that displayed reduced susceptibility to carbapenems but were lacking significant carbapenemase activity as revealed by negative Carba NP test results. However, positive test results were seen for OXA-48-like enzymes by lateral flow immunoassays. WGS revealed the presence of a blaOXA-181-like gene that codes for OXA-484, an R214G variant of OXA-181. BlaOXA-484 gene was located on a 58.4-kb IncP1-like plasmid (pN-OXA-484), that upon transfer into E. coli HB4 with impaired permeability, conferred carbapenem and temocillin resistance (MICs > 32 mg/L). E. coli TOP10 (pTOPO-OXA-484) revealed reduced MICs in most substrates as compared to E. coli TOP10 (pTOPO-OXA-181), especially for imipenem (0.25 mg/L versus 0.75 mg/L) and temocillin (16 mg/L versus 1028 mg/L). Catalytic efficiencies of OXA-484 were reduced as compared to OXA-181 for most ß-lactams including imipenem and temocillin with 27.5- and 21.7-fold reduction, respectively. Molecular modeling confirmed that the salt bridges between R214, D159, and the R1 substituent's carboxylate group of temocillin were not possible with G214 in OXA-484, explaining the reduced affinity for temocillin. In addition, changes in active site's water network may explain the decrease in hydrolysis rate of carbapenems. OXA-484 has weak imipenem and temocillin hydrolytic activities, which may lead to silent spread due to underdetection using selective screening media or biochemical imipenem hydrolysis confirmatory tests. [ABSTRACT FROM AUTHOR]

Published
2024
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7. The emergence of carbapenemase-producing Enterobacterales in hospitals: a major challenge for a debilitated healthcare system in Lebanon

Author

Daaboul, Dina, primary, Oueslati, Saoussen, additional, Rima, Mariam, additional, Kassem, Issmat I., additional, Mallat, Hassan, additional, Birer, Aurélien, additional, Girlich, Delphine, additional, Hamze, Monzer, additional, Dabboussi, Fouad, additional, Osman, Marwan, additional, and Naas, Thierry, additional

Published
2023
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8. Genomic characterization of plasmid-borne colistin resistance variants, mcr-1.1 and mcr-1.26, in multidrug-resistant Escherichia coli isolated from backyard farm animals

Author

Daaboul, Dina, Kassem, Issmat I., El Omari, Khaled, Eltai, Nahla O., Hassan, Jouman, Al Jamal, Hadi, Fayad, Souad, Salma, Rayane, Ghorbani Tajani, Anahita, Bisha, Bledar, Hamze, Monzer, Oueslati, Saoussen, Cummings, Kevin J., Dabboussi, Fouad, Naas, Thierry, and Osman, Marwan

Published
2024
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9. Genomic characterization of an NDM-9-producing Acinetobacter baumannii clinical isolate and role of Glu152Lys substitution in the enhanced cefiderocol hydrolysis of NDM-9

Author

Gaillot, Susie, primary, Oueslati, Saoussen, additional, Vuillemenot, Jean-Baptiste, additional, Bour, Maxime, additional, Iorga, Bogdan I., additional, Triponney, Pauline, additional, Plésiat, Patrick, additional, Bonnin, Rémy A., additional, Naas, Thierry, additional, Jeannot, Katy, additional, and Potron, Anaïs, additional

Published
2023
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12. Evaluation of InTray Cassettes Directly from Blood Cultures for the Diagnosis of Sepsis in Clinical Bacteriology Laboratories as an Alternative to Classic Culture Media

Author

Natale, Alessandra, primary, Oueslati, Saoussen, additional, Rochard, Alice, additional, Ombelet, Sien, additional, Lopez-Baez, Daniel, additional, Hardy, Liselotte, additional, Cunningham, Jane, additional, Franquesa, Céline, additional, Vandenberg, Olivier, additional, Ronat, Jean-Baptiste, additional, and Naas, Thierry, additional

Published
2023
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13. Clinical Added Value of SARS-CoV-2 Antigen Detection in Blood Samples

Author

Oueslati, Saoussen, primary, Manai Bouokazi, Melek, additional, Ramdhani, Ikrame, additional, Escaut, Lélia, additional, Pham, Tài, additional, Ouzani, Souad, additional, Anguel, Nadia, additional, Bulifon, Sophie, additional, Vauloup-Fellous, Christelle, additional, Coilly, Audrey, additional, Legros, Laurence, additional, Guichardon, Magali, additional, Fortineau, Nicolas, additional, Dortet, Laurent, additional, Roque-Afonso, Anne-Marie, additional, and Naas, Thierry, additional

Published
2022
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15. Prevalence and Molecular Mechanisms of Carbapenem Resistance among Gram-Negative Bacilli in Three Hospitals of Northern Lebanon

Author

Rima, Mariam, primary, Oueslati, Saoussen, additional, Dabos, Laura, additional, Daaboul, Dina, additional, Mallat, Hassan, additional, Bou Raad, Elie, additional, Achkar, Marcel, additional, Mawlawi, Osman, additional, Bernabeu, Sandrine, additional, Bonnin, Rémy A., additional, Girlich, Delphine, additional, Osman, Marwan, additional, Hamze, Monzer, additional, and Naas, Thierry, additional

Published
2022
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19. Specificities and Commonalities of Carbapenemase-Producing Escherichia coli Isolated in France from 2012 to 2015

Author

Patiño-Navarrete, Rafael, Rosinski-Chupin, Isabelle, Cabanel, Nicolas, Dieudonné Zongo, Pengdbamba, Héry, Mélanie, Oueslati, Saoussen, Girlich, Delphine, Dortet, Laurent, Bonnin, Rémy, Naas, Thierry, Glaser, Philippe, Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, French National Reference Center for Antibiotic Resistance: Carbapenemase producing Enterobacteriaceae [Le Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), This work was supported by grants from the French National Research Agency (ANR-10-LABX-62-IBEID, ANR-10-LABX-33, INCEPTION project (PIA/ANR-16-CONV-0005)) and from the European Union’s Horizon 2020 research and Innovation Program under grant agrement No 773830 (Project ARDIG, One Health EJP). Pengdbamba Dieudonné Zongo is a scholar of Ed525 CDV, Sorbonne Université, Paris., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-LABX-0033,LERMIT,Research Laboratory on Drugs and Therapeutic Innovation(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Ecologie et Evolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)

Subjects
Carbapenem-Resistant Enterobacteriaceae, multidrug resistance, drug resistance evolution, Escherichia coli, genomics, Humans, emergence, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, France, surveillance studies, Escherichia coli Infections, Phylogeny, Research Article
Abstract

Carbapenemase-producing Escherichia coli (CP-Ec) represents a major public health threat with a risk of dissemination in the community as has occurred for lineages producing extended-spectrum β-lactamases. To characterize the extent of CP-Ec spread in France, isolates from screening and infection samples received at the French National Reference Center (F-NRC) laboratory for carbapenemase-producing Enterobacterales were investigated. A total of 691 CP-Ec isolates collected between 2012 and 2015 and 22 isolates collected before 2012 were fully sequenced. Analysis of their genome sequences revealed some disseminating multidrug-resistant (MDR) lineages frequently acquiring diverse carbapenemase genes mainly belonging to clonal complex 23 (CC23) (sequence type 410 [ST410]) and CC10 (ST10 and ST167) and sporadic isolates, including rare ST131 isolates (n = 17). However, the most represented sequence type (ST) was ST38 (n = 92) with four disseminated lineages carrying blaOXA-48-like genes inserted in the chromosome. Globally, the most frequent carbapenemase gene (n = 457) was blaOXA-48. It was also less frequently associated with MDR isolates being the only resistance gene in 119 isolates. Thus, outside the ST38 clades, its acquisition was frequently sporadic with no sign of dissemination, reflecting the circulation of the IncL plasmid pOXA-48 in France and its high frequency of conjugation. In contrast, blaOXA-181 and blaNDM genes were often associated with the evolution of MDR E. coli lineages characterized by mutations in ftsI and ompC. IMPORTANCE Carbapenemase-producing Escherichia coli (CP-Ec) might be difficult to detect, as MICs can be very low. However, their absolute number and their proportion among carbapenem-resistant Enterobacterales have been increasing, as reported by WHO and national surveillance programs. This suggests a still largely uncharacterized community spread of these isolates. Here, we have characterized the diversity and evolution of CP-Ec isolated in France before 2016. We show that carbapenemase genes are associated with a wide variety of E. coli genomic backgrounds and a small number of dominant phylogenetic lineages. In a significant proportion of CP-Ec, the most frequent carbapenemase gene blaOXA-48, was detected in isolates lacking any other resistance gene, reflecting the dissemination of pOXA-48 plasmids, likely in the absence of any antibiotic pressure. In contrast, carbapenemase gene transfer may also occur in multidrug-resistant E. coli, ultimately giving rise to at-risk lineages encoding carbapenemases with a high potential of dissemination.

Published
2022

24. Rapid Detection of VanA/B-Producing Vancomycin-Resistant Enterococci Using Lateral Flow Immunoassay

Author

Oueslati, Saoussen, primary, Gonzalez, Camille, additional, Volland, Hervé, additional, Cattoir, Vincent, additional, Bernabeu, Sandrine, additional, Girlich, Delphine, additional, Dulac, Duncan, additional, Plaisance, Marc, additional, Boutigny, Laure, additional, Dortet, Laurent, additional, Simon, Stéphanie, additional, and Naas, Thierry, additional

Published
2021
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25. Detection and characterization of VIM-52, a new variant of VIM-1 from clinical isolate

Author

de Barsy, Marie, Mercuri, Paola Sandra, Oueslati, Saoussen, Elisée, Eddy, Huang, Te-Din, Sacré, Pierre, Iorga, Bogdan I, Naas, Thierry, Galleni, Moreno, Bogaerts, Pierre, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Laboratoire de biologie clinique

Abstract

Over the last two decades, antimicrobial resistance has become a global health problem. In Gram-negative bacteria, metallo-β-lactamases (MBLs), which inactivate virtually all β-lactams, increasingly contribute to this phenomenon. The aim of this study is to characterize VIM-52, a His224Arg variant of VIM-1, identified in a clinical isolate. VIM-52 conferred lower MICs to cefepime and ceftazidime as compared to VIM-1. These results were confirmed by steady state kinetic measurements, where VIM-52 yielded a lower activity towards ceftazidime and cefepime but not against carbapenems. Residue 224 is part of the L10 loop (residues 221-241), which borders the active site. As Arg 224 and Ser 228 are both playing an important and interrelated role in enzymatic activity, stability and substrate specificity for the MBLs, targeted mutagenesis at both positions were performed and further confirmed their crucial role for substrate specificity.

Published
2021

26. Validation of Three MicroScan ® Antimicrobial Susceptibility Testing Plates Designed for Low-Resource Settings.

Author

Ronat, Jean-Baptiste, Oueslati, Saoussen, Natale, Alessandra, Kesteman, Thomas, Elamin, Wael, Langendorf, Céline, Hardy, Liselotte, Vandenberg, Olivier, and Naas, Thierry

Subjects
*MICROBIAL sensitivity tests, *GRAM-negative bacteria, *TEST design, *STAPHYLOCOCCUS, *ANTIBIOTICS
Abstract

Easy and robust antimicrobial susceptibility testing (AST) methods are essential in clinical bacteriology laboratories (CBL) in low-resource settings (LRS). We evaluated the Beckman Coulter MicroScan lyophilized broth microdilution panel designed to support Médecins Sans Frontières (MSF) CBL activity in difficult settings, in particular with the Mini-Lab. We evaluated the custom-designed MSF MicroScan Gram-pos microplate (MICPOS1) for Staphylococcus and Enterococcus species, MSF MicroScan Gram-neg microplate (MICNEG1) for Gram-negative bacilli, and MSF MicroScan Fastidious microplate (MICFAST1) for Streptococci and Haemophilus species using 387 isolates from routine CBLs from LRS against the reference methods. Results showed that, for all selected antibiotics on the three panels, the proportion of the category agreement was above 90% and the proportion of major and very major errors was below 3%, as per ISO standards. The use of the Prompt inoculation system was found to increase the MIC and the major error rate for some antibiotics when testing Staphylococci. The readability of the manufacturer's user manual was considered challenging for low-skilled staff. The inoculations and readings of the panels were estimated as easy to use. In conclusion, the three MSF MicroScan MIC panels performed well against clinical isolates from LRS and provided a convenient, robust, and standardized AST method for use in CBL in LRS. [ABSTRACT FROM AUTHOR]

Published
2022
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28. Evaluating 10 Commercially Available SARS-CoV-2 Rapid Serological Tests by Use of the STARD (Standards for Reporting of Diagnostic Accuracy Studies) Method

Author

Dortet, Laurent, primary, Ronat, Jean-Baptiste, additional, Vauloup-Fellous, Christelle, additional, Langendorf, Céline, additional, Mendels, David-Alexis, additional, Emeraud, Cécile, additional, Oueslati, Saoussen, additional, Girlich, Delphine, additional, Chauvin, Anthony, additional, Afdjei, Ali, additional, Bernabeu, Sandrine, additional, Le Pape, Samuel, additional, Kallala, Rim, additional, Rochard, Alice, additional, Verstuyft, Celine, additional, Fortineau, Nicolas, additional, Roque-Afonso, Anne-Marie, additional, and Naas, Thierry, additional

Published
2021
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30. A Lateral Flow Immunoassay for the Rapid Identification of CTX-M-Producing Enterobacterales from Culture Plates and Positive Blood Cultures

Author

Bernabeu, Sandrine, primary, Ratnam, Kayaththiry Caroline, additional, Boutal, Hervé, additional, Gonzalez, Camille, additional, Vogel, Anaïs, additional, Devilliers, Karine, additional, Plaisance, Marc, additional, Oueslati, Saoussen, additional, Malhotra-Kumar, Surbhi, additional, Dortet, Laurent, additional, Fortineau, Nicolas, additional, Simon, Stéphanie, additional, Volland, Hervé, additional, and Naas, Thierry, additional

Published
2020
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31. The Mini-Lab: accessible clinical bacteriology for low-resource settings

Author

Natale, Alessandra, primary, Ronat, Jean-Baptiste, additional, Mazoyer, Albane, additional, Rochard, Alice, additional, Boillot, Baptiste, additional, Hubert, Julie, additional, Baillet, Bernard, additional, Ducasse, Marion, additional, Mantelet, Fabrice, additional, Oueslati, Saoussen, additional, Ombelet, Sien, additional, Langendorf, Céline, additional, Naas, Thierry, additional, Vandenberg, Olivier, additional, and Jacobs, Jan, additional

Published
2020
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32. NMR Characterization of the Influence of Zinc(II) Ions on the Structural and Dynamic Behavior of the New Delhi Metallo-β-Lactamase-1 and on the Binding with Flavonols as Inhibitors

Author

Rivière, Gwladys, primary, Oueslati, Saoussen, additional, Gayral, Maud, additional, Créchet, Jean-Bernard, additional, Nhiri, Naïma, additional, Jacquet, Eric, additional, Cintrat, Jean-Christophe, additional, Giraud, François, additional, van Heijenoort, Carine, additional, Lescop, Ewen, additional, Pethe, Stéphanie, additional, Iorga, Bogdan I., additional, Naas, Thierry, additional, Guittet, Eric, additional, and Morellet, Nelly, additional

Published
2020
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34. Evaluation of the BD MAX Check-Points CPO Assay for the Detection of Carbapenemase Producers Directly from Rectal Swabs

Author

Girlich, Delphine, primary, Oueslati, Saoussen, additional, Bernabeu, Sandrine, additional, Langlois, Isabelle, additional, Begasse, Christine, additional, Arangia, Nicolas, additional, Creton, Elodie, additional, Cotellon, Garance, additional, Sauvadet, Aimie, additional, Dortet, Laurent, additional, Fortineau, Nicolas, additional, and Naas, Thierry, additional

Published
2020
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38. False-Positive Carbapenem-Hydrolyzing Confirmatory Tests Due to ACT-28, a Chromosomally Encoded AmpC with Weak Carbapenemase Activity from Enterobacter kobei

Author

Jousset, Agnès B., primary, Oueslati, Saoussen, additional, Bernabeu, Sandrine, additional, Takissian, Julie, additional, Creton, Elodie, additional, Vogel, Anaïs, additional, Sauvadet, Aimie, additional, Cotellon, Garance, additional, Gauthier, Lauraine, additional, Bonnin, Rémy A., additional, Dortet, Laurent, additional, and Naas, Thierry, additional

Published
2019
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39. Development and validation of a lateral flow immunoassay for rapid detection of NDM-producing Enterobacteriaceae

Author

Boutal, Hervé, Naas, Thierry, Devilliers, Karine, Oueslati, Saoussen, Dortet, Laurent, Bernabeu, Sandrine, Simon, Stéphanie, Volland, Hervé, Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Saclay (COmUE), Université Paris-Sud - Paris 11 (UP11), Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Ministère de l’Education Nationale et de la Recherche [EA7361], Université Paris-Sud, Université Paris Saclay, ANR [ANR-10- LABX-33], Service de Pharmacologie et d'Immunoanalyse (SPI), and Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Carbapenem-Resistant Enterobacteriaceae, Time Factors, [SDV]Life Sciences [q-bio], lateral flow immunoassay, Enterobacteriaceae Infections, detection, Humans, NDM-1, Immunoassays, Sensitivity and Specificity, Chromatography, Affinity, beta-Lactamases
Abstract

International audience; The global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. The NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized β-lactamase gene content and 74 nonduplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for Antibiotic Resistance during a 1-week period (in June 2016). The reference collection included 55 non-carbapenemase producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM-like carbapenemase producers of the reference collection were correctly detected in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2 producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended-spectrum β-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74 referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers were identified. Overall, the sensitivity and specificity of the assay were 100% for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA was efficient, rapid, and easy to implement in the routine workflow of a clinical microbiology laboratory for the confirmation of NDM-like carbapenemase-producing Enterobacteriaceae.

Published
2017

42. Multicentre evaluation of the BYG Carba v2.0 test, a simplified electrochemical assay for the rapid laboratory detection of carbapenemase-producing Enterobacteriaceae

Author

Bogaerts, Pierre, primary, Oueslati, Saoussen, additional, Meunier, Danièle, additional, Nonhoff, Claire, additional, Yunus, Sami, additional, Massart, Marion, additional, Denis, Olivier, additional, Woodford, Neil, additional, Hopkins, Katie L., additional, Naas, Thierry, additional, Dortet, Laurent, additional, Huang, Te-Din, additional, and Glupczynski, Youri, additional

Published
2017
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45. A multiplex lateral flow immunoassay for the rapid identification of NDM-, KPC-, IMP- and VIM-type and OXA-48-like carbapenemase-producing Enterobacteriaceae.

Author

Boutal, Hervé, Vogel, Anaïs, Bernabeu, Sandrine, Devilliers, Karine, Creton, Elodie, Cotellon, Garence, Plaisance, Marc, Oueslati, Saoussen, Dortet, Laurent, Jousset, Agnès, Simon, Stéphanie, Naas, Thierry, and Volland, Hervé

Subjects
CULTURE media (Biology), DIAGNOSTIC errors, DRUG resistance, ENTEROBACTERIACEAE, IMMUNOASSAY, LONGITUDINAL method, MICROBIAL sensitivity tests, RETROSPECTIVE studies, CARBAPENEMS
Abstract

Objectives: The global spread of carbapenemase-producing Enterobacteriaceae represents a substantial challenge in clinical practice and rapid and reliable detection of these organisms is essential. The aim of this study was to develop and validate a lateral flow immunoassay (Carba5) for the detection of the five main carbapenemases (KPC-, NDM-, VIM- and IMP-type and OXA-48-like).Methods: Carba5 was retrospectively and prospectively evaluated using 296 enterobacterial isolates from agar culture. An isolated colony was suspended in extraction buffer and then loaded on the manufactured Carba5.Results: All 185 isolates expressing a carbapenemase related to one of the Carba5 targets were correctly and unambiguously detected in <15 min. All other isolates gave negative results except those producing OXA-163 and OXA-405, which are considered low-activity carbapenemases. No cross-reaction was observed with non-targeted carbapenemases, ESBLs, AmpCs or oxacillinases (OXA-1, -2, -9 and -10). Overall, this assay reached 100% sensitivity and 95.3% (retrospectively) to 100% (prospectively) specificity.Conclusions: Carba5 is efficient, rapid and easy to implement in the routine workflow of a clinical microbiology laboratory for confirmation of the five main carbapenemases encountered in Enterobacteriaceae. [ABSTRACT FROM AUTHOR]

Published
2018
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47. The occurrence of the carbapenemase gene, blaNDM-5, on a transmissible IncX3 plasmid in Multidrug-Resistant Escherichia coliisolated from a Farm Dog

Author

Daaboul, Dina, Kassem, Issmat I., Omari, Khaled El, Dabboussi, Fouad, Oueslati, Saoussen, Naas, Thierry, and Osman, Marwan

Abstract

In depth phenotypic and genomic analyses of a carbapenem-resistant Escherichia coliisolate, recovered from the feces of a farm dog in Lebanon, focusing on its antimicrobial resistance (AMR) patterns and the underlying resistome.

Published
2023
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48. Biochemical and Structural Characterization of OXA-405, an OXA-48 Variant with Extended-Spectrum β-Lactamase Activity.

Author

Oueslati, Saoussen, Retailleau, Pascal, Marchini, Ludovic, Dortet, Laurent, Bonnin, Rémy A., Iorga, Bogdan I., and Naas, Thierry

Subjects
WATER distribution, MOLECULAR dynamics, STRUCTURAL design, WELL water, DRUG resistance in bacteria, BINDING energy, BETA lactamases
Abstract

OXA-48-producing Enterobacterales have now widely disseminated globally. A sign of their extensive spread is the identification of an increasing number of OXA-48 variants. Among them, three are particularly interesting, OXA-163, OXA-247 and OXA-405, since they have lost carbapenem activities and gained expanded-spectrum cephalosporin hydrolytic activity subsequent to a four amino-acid (AA) deletion in the β5–β6 loop. We investigated the mechanisms responsible for substrate specificity of OXA-405. Kinetic parameters confirmed that OXA-405 has a hydrolytic profile compatible with an ESBL (hydrolysis of expanded spectrum cephalosporins and susceptibility to class A inhibitors). Molecular modeling techniques and 3D structure determination show that the overall dimeric structure of OXA-405 is very similar to that of OXA-48, except for the β5–β6 loop, which is shorter for OXA-405, suggesting that the length of the β5–β6 loop is critical for substrate specificity. Covalent docking with selected substrates and molecular dynamics simulations evidenced the structural changes induced by substrate binding, as well as the distribution of water molecules in the active site and their role in substrate hydrolysis. All this data may represent the structural basis for the design of new and efficient class D inhibitors. [ABSTRACT FROM AUTHOR]

Published
2020
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49. Polyclonal Dissemination of NDM-1- and NDM-9-Producing Escherichia coliand Klebsiella pneumoniaein French Polynesia

Author

Oueslati, Saoussen, Emeraud, Cécile, Grosperrin, Victor, Levy, Marc, Cotellon, Garance, Creton, Elodie, Gauthier, Lauraine, Bonnin, Rémy A., Naas, Thierry, and Dortet, Laurent

Abstract

The whole-genome sequencing analysis revealed a polyclonal dissemination of NDM-1 and NDM-9 variants in Escherichia coli(n= 20) and Klebsiella pneumoniae(n= 2) in Tahiti since 2015 via interspecies transfer of three different blaNDM-carrying plasmids (IncR, IncHI2, and IncF) and patient-to-patient cross-transmission. It highlights the potential risk of importation of NDM producers in France, where French Polynesia is not considered stricto sensua foreign country from which repatriated patients have to be screened.

Published
2021
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50. A 2.5-Year Within-Patient Evolution of Pseudomonas aeruginosaIsolates with In VivoAcquisition of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Resistance upon Treatment

Author

Boulant, Thibaud, Jousset, Agnès B., Bonnin, Rémy A., Barrail-Tran, Aurélie, Borgel, Adrien, Oueslati, Saoussen, Naas, Thierry, and Dortet, Laurent

Abstract

Ceftolozane-tazobactam is considered to be a last-resort treatment for infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. Although resistance to this antimicrobial has been described in vitro, the development of resistance in vivohas rarely been reported. Here, we describe the evolution of resistance to ceftolozane-tazobactam of P. aeruginosaisolates recovered from the same patient during recurrent infections over 2.5 years.

Published
2019
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