Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia.
To analyse whether the mutation-driven resistance-acquisition potential of a given bacterium might be a function of its intrinsic resistome, quinolones were used as selective agents and Stenotrophomonas maltophilia was chosen as a bacterial model. S. maltophilia has two elements - SmQnr and SmeDEF - that are important in intrinsic resistance to quinolones. Using a battery of mutants in which either or both of these elements had been removed, the apparent mutation frequency for quinolone resistance and the phenotype of the selected mutants were found to be related to the intrinsic resistome and also depended on the concentration of the selector. Most mutants had phenotypes compatible with the overexpression of multidrug efflux pump(s); SmeDEF overexpression was the most common cause of quinolone resistance. Whole genome sequencing showed that mutations of the SmeRv regulator, which result in the overexpression of the efflux pump SmeVWX, are the cause of quinolone resistance in mutants not overexpressing SmeDEF. These results indicate that the development of mutation-driven antibiotic resistance is highly dependent on the intrinsic resistome, which, at least for synthetic antibiotics such as quinolones, did not develop as a response to the presence of antibiotics in the natural ecosystems in which S. maltophilia evolved.
Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Darwin 3, Cantoblanco, Madrid, 28049, Spain.
Guillermo
G
García-León
Fabiola
F
Salgado
Juan Carlos
JC
Oliveros
María Blanca
MB
Sánchez
José Luis
JL
Martínez
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D026901:Membrane Transport Proteins / Q000378:metabolism; D009154:Mutation; D015363:Quinolones / Q000494:pharmacology*; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D015363:Quinolones; C417265:SmeD protein, Stenotrophomonas maltophilia; C417266:SmeE protein, Stenotrophomonas maltophilia; C417267:SmeF protein, Stenotrophomonas maltophilia