Mutant prevention concentrations of fluoroquinolones against Campylobacter jejuni isolated from chicken.
The mutant prevention concentration (MPC) and mutant selection window (MSW) concepts have been used to evaluate antibiotic concentration ranges that prevent the emergence of antibiotic resistant mutants. Campylobacter jejuni is highly mutable to fluoroquinolone (FQ) antibiotics, but it is unknown if the MPC concept can be used to prevent mutant emergence. In this study, the MPCs of three FQs including enrofloxacin, norfloxacin and ciprofloxacin were determined using 13 C. jejuni isolates. Also, first- and second-step FQ-resistant mutants were selected and the mutations in gyrA and gyrB as well as the contribution of efflux pump to FQ resistance were investigated. The MICs of all selected mutants were determined in the presence or absence of the efflux pump inhibitors carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and reserpine. Our results revealed that the three tested FQs had different MPC ranges and the MPC order was norfloxacin > ciprofloxacin > enrofloxacin, suggesting a better in vitro efficacy of enrofloxacin over ciprofloxacin and norfloxacin in reducing the emergence of C. jejuni mutants. The results also confirmed the single-step mechanism of acquired FQs resistance in C. jejuni mutants. Both point mutations (Thr-86-Ile and Asp-90-Asn) in the gyrA gene and the function of efflux pumps contributed to the acquired resistance to ciprofloxacin and norfloxacin, while gyrA mutations (Thr-86-Ile and Asp-90-Asn) were the main mechanism for enrofloxacin resistance. These findings provide new insights into the development and mechanisms of FQ resistance in Campylobacter.
College of Veterinary Medicine, Nanjing Agricultural University, Tongwei Road 6, Nanjing, Jiangsu Province 210095, PR China. wlp71@163.com
Liping
L
Wang
Zhang
Z
Yuanshu
Zhang
Z
Yuhan
Yaojie
Li
L
Yingxia
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002169:Campylobacter Infections / Q000382:microbiology / Q000662:veterinary*; D016123:Campylobacter jejuni / Q000145:classification / Q000187:drug effects*; D002645:Chickens; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011201:Poultry Diseases / Q000382:microbiology
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase