Transferable quinolone resistance in Vibrio cholerae.
Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera.
Kim
Hong Bin
HB
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Wang
Minghua
M
Ahmed
Sabeena
S
Park
Chi Hye
CH
LaRocque
Regina C
RC
Faruque
Abu S G
AS
Salam
Mohammed A
MA
Khan
Wasif A
WA
Qadri
Firdausi
F
Calderwood
Stephen B
SB
Jacoby
George A
GA
Hooper
David C
DC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002876:Chromosomes, Bacterial / Q000235:genetics; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics / Q000502:physiology; D027101:DNA Topoisomerase IV / Q000235:genetics / Q000502:physiology; D004251:DNA Transposable Elements / Q000235:genetics / Q000502:physiology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D016133:Polymerase Chain Reaction; D015363:Quinolones / Q000494:pharmacology*; D014734:Vibrio cholerae / Q000187:drug effects* / Q000235:genetics*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D015363:Quinolones; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase