Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials
| Autor: | Karine Gloux, Sophie Brinster, Constantin Hays, Gilles Lamberet, Gérald Kénanian, Jamila Anba-Mondoloni, Sean Kennedy, Alexandra Gruss, Claire Poyart, David Halpern, Patrick Trieu-Cuot, Claire Morvan |
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| Přispěvatelé: | MICrobiologie de l'ALImentation au Service de la Santé humaine (MICALIS), Institut National de la Recherche Agronomique (INRA) - AgroParisTech, Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), This work was supported by Agence Nationale de la Recherche (ANR) funding of the FattyBact project ANR-132101, TRIEU-CUOT, Patrick, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Gruss, Alexandra |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mutant General Physics and Astronomy medicine.disease_cause [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Mice [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Fatty Acid Synthase Type II Cloning Molecular [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] chemistry.chemical_classification Mice Inbred BALB C Multidisciplinary Virulence Escherichia coli Proteins Fatty Acids Antimicrobial Anti-Bacterial Agents 3. Good health [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Biochemistry Staphylococcus aureus [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Female Science 030106 microbiology Biology Article General Biochemistry Genetics and Molecular Biology Microbiology 03 medical and health sciences [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Drug Resistance Bacterial Acyl-Carrier Protein S-Malonyltransferase medicine Animals [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Gene Alleles Polymorphism Genetic Lipogenesis Genetic Complementation Test Fatty acid [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Sequence Analysis DNA General Chemistry biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Triclosan Enzyme chemistry Mutation [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Bacteria |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2016, 7, pp.12944 Nature Communications, 2016, 7, pp.12944. ⟨10.1038/ncomms12944⟩ Nature Communications, Nature Publishing Group, 2016, 7, pp.12944. ⟨10.1038/ncomms12944⟩ Nature Communications, Vol 7, Iss 1, Pp 1-11 (2016) Nature Communications (7), 12944. (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms12944⟩ |
| Popis: | The bacterial pathway for fatty acid biosynthesis, FASII, is a target for development of new anti-staphylococcal drugs. This strategy is based on previous reports indicating that self-synthesized fatty acids appear to be indispensable for Staphylococcus aureus growth and virulence, although other bacteria can use exogenous fatty acids to compensate FASII inhibition. Here we report that staphylococci can become resistant to the FASII-targeted inhibitor triclosan via high frequency mutations in fabD, one of the FASII genes. The fabD mutants can be conditional for FASII and not require exogenous fatty acids for normal growth, and can use diverse fatty acid combinations (including host fatty acids) when FASII is blocked. These mutants show cross-resistance to inhibitors of other FASII enzymes and are infectious in mice. Clinical isolates bearing fabD polymorphisms also bypass FASII inhibition. We propose that fatty acid-rich environments within the host, in the presence of FASII inhibitors, might favour the emergence of staphylococcal strains displaying resistance to multiple FASII inhibitors. The bacterial pathway for fatty acid biosynthesis, FASII, is a target for development of new anti-staphylococcal drugs. Here, Morvan et al. show that exogenous fatty acids can favour the emergence of staphylococcal strains displaying resistance to multiple FASII inhibitors. |
| Databáze: | OpenAIRE |
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