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3. Insights into the anticancer properties of the first antimicrobial peptide from Archaea

Author

Gaglione, Rosa, Pirone, Luciano, Farina, Biancamaria, Fusco, Salvatore, Smaldone, Giovanni, Aulitto, Martina, Dell'Olmo, Eliana, Roscetto, Emanuela, Del Gatto, Annarita, Fattorusso, Roberto, Notomista, Eugenio, Zaccaro, Laura, Arciello, Angela, Pedone, Emilia, and Contursi, Patrizia

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cancer, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Antimicrobial Cationic Peptides, Antineoplastic Agents, BALB 3T3 Cells, Cell Death, Cell Membrane, Circular Dichroism, Humans, Mice, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Sulfolobus, Antimicrobial peptide, Anticancer peptide, Archaea, Peptide-membrane interactions, Pharmacology and Pharmaceutical Sciences, Biochemistry & Molecular Biology, Biochemistry and cell biology
Abstract

BackgroundThe peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial peptide, possessing a broad-spectrum antibacterial activity.MethodsThrough a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied.ResultsIt is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and human tumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways.ConclusionsVLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and human cancer cells and consequently can be classified as an ACP.General significanceVLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity.

Published
2017

5. Multicenter study on the prevalence of colonization due to carbapenem-resistant Enterobacterales strains before and during the first year of COVID-19, Italy 2018–2020

Author

Fasciana, Teresa, primary, Antonelli, Alberto, additional, Bianco, Gabriele, additional, Lombardo, Donatella, additional, Codda, Giulia, additional, Roscetto, Emanuela, additional, Perez, Marianna, additional, Lipari, Dario, additional, Arrigo, Ignazio, additional, Galia, Elena, additional, Tricoli, Maria Rita, additional, Calvo, Maddalena, additional, Niccolai, Claudia, additional, Morecchiato, Fabio, additional, Errico, Giulia, additional, Stefani, Stefania, additional, Cavallo, Rossana, additional, Marchese, Anna, additional, Catania, Maria Rosaria, additional, Ambretti, Simone, additional, Rossolini, Gian Maria, additional, Pantosti, Annalisa, additional, Palamara, Anna Teresa, additional, Sabbatucci, Michela, additional, Serra, Nicola, additional, and Giammanco, Anna, additional

Published
2023
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6. Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired Staphylococcus aureus Infections

Author

Folliero, Veronica, primary, Dell’Annunziata, Federica, additional, Santella, Biagio, additional, Roscetto, Emanuela, additional, Zannella, Carla, additional, Capuano, Nicoletta, additional, Perrella, Alessandro, additional, De Filippis, Anna, additional, Boccia, Giovanni, additional, Catania, Maria Rosaria, additional, Galdiero, Massimiliano, additional, and Franci, Gianluigi, additional

Published
2023
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8. Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans.

Author

Bellavita, Rosa, Falanga, Annarita, Merlino, Francesco, D'Auria, Gabriella, Molfetta, Nicola, Saviano, Anella, Maione, Francesco, Galdiero, Umberto, Catania, Maria Rosaria, Galdiero, Stefania, Grieco, Paolo, Roscetto, Emanuela, Falcigno, Lucia, and Buommino, Elisabetta

Subjects
CANDIDA albicans, BILAYER lipid membranes, FUNGAL membranes, ELECTROSTATIC interaction, CYTOTOXINS, CONFOCAL microscopy
Abstract

The increasing resistance of fungi to conventional antifungal drugs has prompted worldwide the search for new compounds. In this work, we investigated the antifungal properties of acylated Temporin L derivatives, Pent-1B and Dec-1B, against Candida albicans, including the multidrug-resistant strains. Acylated peptides resulted to be active both on reference and clinical strains with MIC values ranging from 6.5 to 26 µM, and they did not show cytotoxicity on human keratinocytes. In addition, we also observed a synergistic or additive effect with voriconazole for peptides Dec-1B and Pent-1B through the checkerboard assay on voriconazole-resistant Candida strains. Moreover, fluorescence-based assays, NMR spectroscopy, and confocal microscopy elucidated a potential membrane-active mechanism, consisting of an initial electrostatic interaction of acylated peptides with fungal membrane, followed by aggregation and insertion into the lipid bilayer and causing membrane perturbation probably through a carpeting effect. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans

Author

Bellavita, Rosa, primary, Falanga, Annarita, additional, Merlino, Francesco, additional, D’Auria, Gabriella, additional, Molfetta, Nicola, additional, Saviano, Anella, additional, Maione, Francesco, additional, Galdiero, Umberto, additional, Catania, Maria Rosaria, additional, Galdiero, Stefania, additional, Grieco, Paolo, additional, Roscetto, Emanuela, additional, Falcigno, Lucia, additional, and Buommino, Elisabetta, additional

Published
2022
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14. Niclosamide as a Repurposing Drug against Corynebacterium striatum Multidrug-Resistant Infections

Author

Folliero, Veronica, primary, Dell’Annunziata, Federica, additional, Roscetto, Emanuela, additional, Cammarota, Marcella, additional, De Filippis, Anna, additional, Schiraldi, Chiara, additional, Catania, Maria Rosaria, additional, Casolaro, Vincenzo, additional, Perrella, Alessandro, additional, Galdiero, Massimiliano, additional, and Franci, Gianluigi, additional

Published
2022
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18. Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves.

Author

Cattaneo, Letizia, Buonomo, Antonio Riccardo, Iacovazzo, Carmine, Giaccone, Agnese, Scotto, Riccardo, Viceconte, Giulio, Mercinelli, Simona, Vargas, Maria, Roscetto, Emanuela, Cacciatore, Francesco, Salvatore, Paola, Catania, Maria Rosaria, Villari, Riccardo, Cittadini, Antonio, and Gentile, Ivan

Subjects
MYCOSES, PNEUMOCYSTIS pneumonia, PULMONARY aspergillosis, HOSPITAL patients, COMMUNICABLE diseases, COVID-19, MEDICAL personnel
Abstract

Invasive fungal infections (IFIs) represent a severe complication of COVID-19, yet they are under-estimated. We conducted a retrospective analysis including all the COVID-19 patients admitted to the Infectious Diseases Unit of the Federico II University Hospital of Naples until the 1 July 2021. Among 409 patients, we reported seven cases of IFIs by Candida spp., seven of Pneumocystis jirovecii pneumonia, three of invasive pulmonary aspergillosis, and one of Trichosporon asahii. None of the cases presented underlying predisposing conditions, excluding one oncohematological patient treated with rituximab. Ten cases showed lymphopenia with high rates of CD4+ < 200/µL. All cases received high-dose steroid therapy (mean duration 33 days, mean cumulative dosage 1015 mg of prednisone equivalent), and seven cases had severe COVID-19 disease (OSCI ≥ 5) prior to IFI diagnosis. The cases showed a higher overall duration of hospitalization (63 vs 24 days) and higher mortality rate (23% vs. 7%) compared with the COVID-19 patients who did not developed IFIs. Cases showed a higher prevalence of high-dose steroid therapy and lymphopenia with CD4+ < 200/µL, primarily due to SARS-CoV-2 infection and not related to underlying comorbidities. IFIs strongly impact the overall length of hospitalization and mortality. Therefore, clinicians should maintain a high degree of suspicion of IFIs, especially in severe COVID-19 patients. [ABSTRACT FROM AUTHOR]

Published
2023
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25. PCR-based rapid genotyping of Stenotrophomonas maltophilia isolates

Author

Zarrilli Raffaele, Casalino Mariassunta, Colonna Bianca, Carlomagno M Stella, Rocco Francesco, Roscetto Emanuela, and Di Nocera Pier

Subjects
Microbiology, QR1-502
Abstract

Abstract Background All bacterial genomes contain repetitive sequences which are members of specific DNA families. Such repeats may occur as single units, or found clustered in multiple copies in a head-to-tail configuration at specific loci. The number of clustered units per locus is a strain-defining parameter. Assessing the length variability of clusters of repeats is a versatile typing methodology known as multilocus variable number of tandem repeat analysis (MLVA). Results Stenotrophomonas maltophilia is an environmental bacterium increasingly involved in nosocomial infections and resistant to most antibiotics. The availability of the whole DNA sequence of the S. maltophilia strain K279a allowed us to set up fast and accurate PCR-based diagnostic protocols based on the measurement of length variations of loci carrying a variable number of short palindromic repeats marking the S. maltophilia genome. On the basis of the amplimers size, it was possible to deduce the number of repeats present at 12 different loci in a collection of S. maltophilia isolates, and therefore label each of them with a digit. PCR-negative regions were labelled 0. Co-amplification of two pairs of loci provided a 4-digit code sufficient for immediate subtyping. By increasing the number of loci analyzed, it should be possible to assign a more specific digit profile to isolates. In general, MLVA data match genotyping data obtained by PFGE (pulsed-field gel electrophoresis). However, some isolates exhibiting the same PCR profiles at all loci display distinct PFGE patterns. Conclusion The utilization of the present protocol allows to type several S. maltophilia isolates in hours. The results are immediately interpretable without the need for sophisticated softwares. The data can be easily reproducible, and compared among different laboratories.

Published
2008
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28. Additional file 8: of Biofilm-associated proteins: news from Acinetobacter

Author

Gregorio, Eliana De, Mariateresa Del Franco, Martinucci, Marianna, Roscetto, Emanuela, Zarrilli, Raffaele, and Nocera, Pier Di

Subjects
polycyclic compounds, bacteria, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

BLP1 empty chromosomal site A) DNA replacing BLP1 coding sequences in BLP1-negative strains. B) Alignment of BLP1 gene empty sites in A. baumannii and non-baumannii species. (DOCX 125Â kb)

Published
2015
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32. Additional file 6: of Biofilm-associated proteins: news from Acinetobacter

Author

Gregorio, Eliana De, Mariateresa Del Franco, Martinucci, Marianna, Roscetto, Emanuela, Zarrilli, Raffaele, and Nocera, Pier Di

Subjects
fungi, polycyclic compounds, bacteria, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses
Abstract

Alpha and beta-BAP genes regions in A. baumannii SDF, A. calcoaceticus PHEA-2, A. baumannii AYE and A. baylyi ADP1 strains. (PDF 39Â kb)

Published
2015
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34. Functional Characterization of the RNA Chaperone Hfq in the Opportunistic Human Pathogen Stenotrophomonas maltophilia. [*Roscetto M, *Angrisano T, co-first authors]

Author

ROSCETTO, EMANUELA, ANGRISANO, TIZIANA, Costa V, Casalino M, Förstner KU, Sharma CM, DI NOCERA, PIERPAOLO, DE GREGORIO, ELIANA, Roscetto, Emanuela, Angrisano, Tiziana, Costa, V, Casalino, M, Förstner, Ku, Sharma, Cm, DI NOCERA, Pierpaolo, and DE GREGORIO, Eliana

Subjects
Espressione genica, non-coding RNA, regolazione post-trascrizionale, small RNA, RNA sequencing, RNA binding protein
Abstract

Hfq is an RNA-binding protein known to regulate a variety of cellular processes by interacting with small RNAs (sRNAs) and mRNAs in prokaryotes. Stenotrophomonas maltophilia is an important opportunistic pathogen affecting primarily hospitalized and immunocompromised hosts. We constructed an hfq deletion mutant (Δhfq) of S. maltophilia and compared the behaviors of wild-type and Δhfq S. maltophilia cells in a variety of assays. This revealed that S. maltophilia Hfq plays a role in biofilm formation and cell motility, as well as susceptibility to antimicrobial agents. Moreover, Hfq is crucial for adhesion to bronchial epithelial cells and is required for the replication of S. maltophilia in macrophages. Differential RNA sequencing analysis (dRNA-seq) of RNA isolated from S. maltophilia wild-type and Δhfq strains showed that Hfq regulates the expression of genes encoding flagellar and fimbrial components, transmembrane proteins, and enzymes involved in different metabolic pathways. Moreover, we analyzed the expression of several sRNAs identified by dRNA-seq in wild-type and Δhfq S. maltophilia cells grown in different conditions on Northern blots. The accumulation of two sRNAs was strongly reduced in the absence of Hfq. Furthermore, based on our dRNA-seq analysis we provide a genome-wide map of transcriptional start sites in S. maltophilia.

Published
2012

35. Proton pump inhibitors as a risk factor for paediatric Clostridium difficile infection

Author

Turco R., Martinelli M., MIELE, ERASMO, ROSCETTO, EMANUELA, DEL PEZZO, MARIASSUNTA, GRECO, LUIGI, STAIANO, ANNAMARIA, Turco, R., Martinelli, M., Miele, Erasmo, Roscetto, Emanuela, DEL PEZZO, Mariassunta, Greco, Luigi, and Staiano, Annamaria

Subjects
Diarrhea, Male, Adolescent, Histamine H2 Antagonists, Clostridioides difficile, Child, Preschool, Humans, Infant, Female, Proton Pump Inhibitors, Child, Epidemiologic Methods, Enterocolitis, Pseudomembranous
Abstract

BACKGROUND: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs) may play an important role on the onset of Clostridium difficile-associated disease (CDAD) in adults. The impact of Clostridium difficile on children treated with gastric acid-suppressing agents remains unknown. AIM: To investigate the relationship between CDAD and exposure to acid suppressive therapy in hospitalized paediatric patients. METHODS: We reviewed the medical records of children, with a diagnosis of protracted diarrhoea and abdominal pain, whose stool was analysed for C. difficile toxins. We identified 68 patients with CDAD. For each patient, we randomly selected one control subjects with stool analysis negative for C. difficile. Comorbid illnesses, previous hospitalizations, antibiotics, corticosteroids, immunosuppressants and gastric acid suppressing exposures were recorded. RESULTS: The use of PPI was significantly higher in C. difficile positive group compared with C. difficile negative group [odds ratio (OR): = 4.5; 95% confidence interval (CI) = 1.4-14.4]. We also found a trend for the use of H(2)RAs in patients infected by C. difficile compared with C. difficile negative comparison group (OR: = 3.8; 95% CI = 0.7-18.9). CONCLUSIONS: Children exposed to PPIs therapy seem to be at higher risk for the development of Clostridium difficile-associated disease.

Published
2010

42. Determination of theIn VitroandIn VivoAntimicrobial Activity on Salivary Streptococci and Lactobacilli and Chemical Characterisation of the Phenolic Content of aPlantago lanceolataInfusion

Author

Ferrazzano, Gianmaria Fabrizio, primary, Cantile, Tiziana, additional, Roberto, Lia, additional, Ingenito, Aniello, additional, Catania, Maria Rosaria, additional, Roscetto, Emanuela, additional, Palumbo, Giuseppe, additional, Zarrelli, Armando, additional, and Pollio, Antonino, additional

Published
2015
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43. Stenotrophomonas maltophilia in nosocomial infections: PCR-based rapid genotyping and mechanisms of pathogenicity

Author

Roscetto, Emanuela and Roscetto, Emanuela

Abstract

Stenotrophomonas maltophilia is an environmental multi-drug-resistant bacterium increasingly involved in nosocomial infections. The role of this opportunistic pathogen in cystic fibrosis has not yet been clearly established, but its involvement in the pathogenesis of very severe infections in immunocompromised patients has been demonstrated. The former aim of this work has been for the first time the setting up of a genotyping method known as MultiLocus Variable number of tandem repeat Analysis (MLVA) for Stenotrophomonas maltophilia. The availability of the whole DNA sequence of the S. maltophilia strain K279a allowed us to set up a fast and accurate PCR-based diagnostic protocol relied on the measurement of length variations of loci carrying a variable number of short palindromic repeats marking the S. maltophilia genome. The utilization of the present protocol allows to type several S. maltophilia isolates in hours. The results are immediately interpretable without the need for sophisticated softwares. The data can be easily reproducible, and compared among different laboratories. The latter aim of this work has been the study of mechanisms of pathogenicity of S. maltophilia, assessing in vitro interactions of environmental and clinical S. maltophilia strains with monocyte-derived dendritic cells (DCs). Our data suggest that the internalization, the intracellular survival and the ability to interfere with normal DCs maturation of S. maltophilia are deeply strain-dependent. We believe that the ability of some tested strains to subvert DC function may be relevant in the pathogenesis of S. maltophilia infections in immunocompromised patients and in patients with cystic fibrosis. Therefore further investigations will be needed to test whether DCs exposed to these bacteria are still able to induce naïve T lymphocytes activation.

Published
2010

45. Screening and Scoring of Antimicrobial and Biological Activities of Italian Vulnerary Plants against Major Oral Pathogenic Bacteria

Author

Ferrazzano, Gianmaria F., primary, Roberto, Lia, additional, Catania, Maria Rosaria, additional, Chiaviello, Angela, additional, De Natale, Antonino, additional, Roscetto, Emanuela, additional, Pinto, Gabriele, additional, Pollio, Antonino, additional, Ingenito, Aniello, additional, and Palumbo, Giuseppe, additional

Published
2013
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46. Isolation of Enterobacter aerogenes carrying bla TEM-1 and bla KPC-3 genes recovered from a hospital Intensive Care Unit.

Author

Pulcrano, Giovanna, Pignanelli, Salvatore, Vollaro, Adriana, Esposito, Matilde, Iula, Vita Dora, Roscetto, Emanuela, Soriano, Amata Amy, and Catania, Maria Rosaria

Subjects
ENTEROBACTER aerogenes, KLEBSIELLA pneumoniae, NOSOCOMIAL infections, INTENSIVE care units, CARBAPENEMS
Abstract

Enterobacter aerogenes has recently emerged as an important hospital pathogen. In this study, we showed the emergence of E. aerogenes isolates carrying the bla KPC gene in patients colonized by carbapenem-resistant Klebsiella pneumoniae strains. Two multiresistant E. aerogenes isolates were recovered from bronchial aspirates of two patients hospitalized in the Intensive Care Unit at the 'Santa Maria della Scaletta' Hospital, Imola. The antimicrobial susceptibility test showed the high resistance to carbapenems and double-disk synergy test confirmed the phenotype of KPC and AmpC production. Other investigation revealed that ESBL and bla KPC genes were carried on the conjugative pKpQIL plasmid. This is a relevant report in Italy that describes a nosocomial infection due to the production of KPC beta-lactamases by an E. aerogenes isolate in patients previously colonized by K. pneumoniae carbapenem-resistant. In conclusion, it's necessary a continuous monitoring of multidrug-resistant strains for the detection of any KPC-producing bacteria that could expand the circulation of carbapenem-resistant pathogens. [ABSTRACT FROM AUTHOR]

Published
2016
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