Impact of ciprofloxacin exposure on Staphylococcus aureus genomic alterations linked with emergence of rifampin resistance

Article Article scientifique Article Impact of ciprofloxacin exposure on Staphylococcus aureus genomic alterations linked with emergence of rifampin resistance eng 2011 author Didier Jean-Philippe 713912 author Villet Régis 684918 author Huggler-kalecinski Elzbieta Maria 26312 author Lew Daniel Pablo 26516 author Hooper David C author Kelley William 28396 author Vaudaux Pierre 24012 1946-1952 10.1128/AAC.01407-10 21357297 0066-4804 Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of Staphylococcus aureus but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) strains exposed in vitro to sub-MICs of ciprofloxacin. Growth of ciprofloxacin-susceptible MRSA strain MRGR3 and ciprofloxacin-resistant MSSA strain RA1 (a NCTC 8325 derivative) in the presence of 1/2× or 1/4× MIC of ciprofloxacin led to higher frequencies of rifampin-resistant mutants on agar supplemented with rifampin (0.25 mg/liter) than under ciprofloxacin-free conditions. While rifampin-resistant mutants from ciprofloxacin-free cultures essentially showed single-amino-acid substitutions, a significant proportion of rifampin-resistant mutants from ciprofloxacin-exposed cultures displayed in-frame deletions or insertions in the rpoB gene at several positions of the rifampin resistance cluster I. In-frame deletions or insertions were also recorded in rpoB cluster I of rifampin-resistant mutants from ciprofloxacin-exposed cultures of mutS and mutL DNA repair mutants of ciprofloxacin-resistant S. aureus strain RA1. Frequencies of rifampin-resistant mutants grown under ciprofloxacin-free medium were higher for mutant strains RA1 mutS2 and RA1 mutL, but not RA1 recA, than for their parent RA1. In conclusion, ciprofloxacin-mediated DNA damage in S. aureus, as exemplified by the wide diversity of deletions or insertions in rpoB, suggests the occurrence of major, quinolone-mediated disturbances in DNA fork progression and replication repair. Besides promoting antibiotic resistance, accumulation of unrepaired DNA replication errors, including insertions and deletions, may also contribute to potentially lethal mutations. Anti-Bacterial Agents/pharmacology Ciprofloxacin/pharmacology Drug Resistance, Bacterial/genetics Microbial Sensitivity Tests Rifampin/pharmacology Staphylococcus aureus/drug effects Dewey 616 54 Département de microbiologie et médecine moléculaire 21B 56 Département de médecine 221 false 63 Acquisition et expression de facteurs de virulence chez Staphylococcus aureus 86 19 Glycopeptide résistance 28 Antimicrobial agents and chemotherapy 55 5 b77e3fcf-dd2a-436e-8a58-c36c233c9e09 Article (Published version) Restricted 2011_Didier_Antimicrob_AgentsChemother_1946-52.pdf 169552 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de médecine

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Impact of ciprofloxacin exposure on Staphylococcus aureus genomic alterations linked with emergence of rifampin resistance	Antimicrobial agents and chemotherapy			2011	747	1

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