Resistance to fluoroquinolones linked to gyrA and par C mutations and overexpression of acr AB efflux pump in Salmonella enterica serotype Choleraesuis.
Between 2000 and 2002, 60 clinical isolates of Salmonella enterica serotype Choleraesuis were collected to investigate the mechanism of fluoroquinolone resistance. PCR and sequencing were performed to identify mutations in gyrA, gyrB, par C, the Acr AB-TolC efflux pump regulator, acr R, and the global regulons mar RAB and sox RS. All resistant strains showed mutations in the target genes leading to amino acid changes of Ser 83 Phe and Asp 87 Asn in GyrA and Ser 80 Ile in Par C. A mutation in gyrB was linked to the serotype genetic diversity but not to fluoroquinolone resistance. An efflux pump inhibitor, Phe-Arg-beta-naphthylamide, caused fourfold lower MIC of ciprofloxacin in the resistant isolates, indicating that efflux systems are involved in fluoroquinolone resistance. Western blot analysis showed moderate overproduction of Acr A in fluoroquinolone- resistant isolates. A mutation in acr R gave rise to an internal stop codon in both ciprofloxacin-resistant and -susceptible isolates, suggesting another serotype genetic diversity. No mutations were detected in mar RAB and sox RS among the isolates examined. Cross-resistance to three fluoroquinolones was observed, but gatifloxacin demonstrated relatively lower MICs than those of ciprofloxacin and levofloxacin. Fluoroquinolone resistance in S. Choleraesuis appears to be the combination effect of multiple mutations in various target genes and overexpression of the Acr AB-TolC efflux pump.
Chu
Chishih
C
Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan.
Su
Lin-Hui
LH
Chu
Chi-Hung
CH
Baucheron
Sylvie
S
Cloeckaert
Axel
A
Chiu
Cheng-Hsun
CH
D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D019779:Salmonella enterica / Q000187:drug effects* / Q000201:enzymology
D002352:Carrier Proteins; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase