Fitness cost of antibiotic susceptibility during bacterial infection
| Autor: | Yang Fu, Hugues Aschard, John J. Mekalanos, François Angoulvant, Stephen Lory, David Skurnik, Jean-Damien Ricard, Gerald B. Pier, Olga Danilchanka, Jonathan Messika, Thomas Guillard, Damien Roux, Vincent Cattoir |
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| Přispěvatelé: | Entérobactéries Résistance Acquise - EA 4687 (ERA), 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), Harvard Medical School [Boston] (HMS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2015 |
| Předmět: |
Acinetobacter baumannii
MESH: Sequence Analysis DNA MESH: Drug Resistance Microbial [SDV]Life Sciences [q-bio] Antibiotics Colony Count Microbial MESH: Rabbits medicine.disease_cause Mice Cost of Illness MESH: Animals Lung Vibrio cholerae ComputingMilieux_MISCELLANEOUS MESH: Microbial Sensitivity Tests [STAT.AP]Statistics [stat]/Applications [stat.AP] biology Drug Resistance Microbial General Medicine Bacterial Infections MESH: Cost of Illness 3. Good health Anti-Bacterial Agents MESH: DNA Transposable Elements MESH: Pseudomonas aeruginosa Pseudomonas aeruginosa Rabbits MESH: Genes Bacterial [STAT.ME]Statistics [stat]/Methodology [stat.ME] MESH: Operon MESH: Pneumonia MESH: Mutation MESH: Bacterial Infections medicine.drug_class Virulence Microbial Sensitivity Tests Microbiology Antibiotic resistance MESH: Anti-Bacterial Agents Operon medicine Animals MESH: Lung MESH: Colony Count Microbial MESH: Mice Gene MESH: Acinetobacter baumannii Pathogenic bacteria Pneumonia Sequence Analysis DNA biology.organism_classification Gastrointestinal Tract Disease Models Animal Mutagenesis Insertional MESH: Mutagenesis Insertional [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Genes Bacterial Mutation DNA Transposable Elements MESH: Gastrointestinal Tract [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie MESH: Disease Models Animal [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] MESH: Vibrio cholerae |
| Zdroj: | Science Translational Medicine Science Translational Medicine, American Association for the Advancement of Science, 2015, 7 (297), pp.297ra114-297ra114. ⟨10.1126/scitranslmed.aab1621⟩ |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aab1621⟩ |
| Popis: | International audience; Advances in high-throughput DNA sequencing allow for a comprehensive analysis of bacterial genes that contribute to virulence in a specific infectious setting. Such information can yield new insights that affect decisions on how to best manage major public health issues such as the threat posed by increasing antimicrobial drug resistance. Much of the focus has been on the consequences of the selective advantage conferred on drug-resistant strains during antibiotic therapy. It is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. However, experimental validation of this accepted paradigm is modest. Using a saturated transposon library of Pseudomonas aeruginosa, we identified genes across many functional categories and operons that contributed to maximal in vivo fitness during lung infections in animal models. Genes that bestowed both intrinsic and acquired antibiotic resistance provided a positive in vivo fitness advantage to P. aeruginosa during infection. We confirmed these findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae using murine and rabbit infection models, respectively. Our results show that efforts to confront the worldwide increase in antibiotic resistance might be exacerbated by fitness advantages that enhance virulence in drug-resistant microbes. |
| Databáze: | OpenAIRE |
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