Scientific article

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

Published inAntimicrobial agents and chemotherapy, vol. 55, no. 5, p. 1946-1952
Publication date2011

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
Citation (ISO format)
DIDIER, Jean-Philippe et al. Impact of ciprofloxacin exposure on Staphylococcus aureus genomic alterations linked with emergence of rifampin resistance. In: Antimicrobial agents and chemotherapy, 2011, vol. 55, n° 5, p. 1946–1952. doi: 10.1128/AAC.01407-10
Main files (1)
Article (Published version)
ISSN of the journal0066-4804

Technical informations

Creation10/23/2012 2:00:00 PM
First validation10/23/2012 2:00:00 PM
Update time03/14/2023 5:49:02 PM
Status update03/14/2023 5:49:02 PM
Last indexation08/29/2023 5:27:27 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack