Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in Escherichia coli Isolated from Dogs and Humans
Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in Escherichia coli Isolated from Dogs and Humans
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DOI：
10.1292/jvms.12-0186
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发表时间：
2013-04-01
影响因子：
1.2
通讯作者：
Tamura, Yutaka
中科院分区：
文献类型：
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作者：
Sato, Toyotaka;Yokota, Shin-ichi;Tamura, Yutaka
大肠埃希菌对氟喹诺酮类药物的耐药主要是由DNA旋转酶和拓扑异构酶IV的喹诺酮类药物耐药决定区突变引起的。AcrAB-TolC外排泵有助于对氟喹诺酮和其他抗菌药物产生耐药性。在这项研究中，我们调查了一个高层次的机制，氟喹诺酮耐药的大肠杆菌。从人临床样品和犬粪便样品中分离的大肠杆菌。E.已经发现具有高水平氟喹诺酮抗性的大肠杆菌菌株经常对头孢菌素类具有抗性。具有高水平氟喹诺酮耐药性的菌株表现出较低的细胞内恩诺沙星（ENR）浓度，较高的AcrA表达，以及用外排泵抑制剂治疗时氟喹诺酮最低抑制浓度的更大降低。结果表明，ENR抗性增强株的出现频率和E.大肠杆菌在ENR存在下的体外表达与亲本菌株中AcrA蛋白表达水平具有良好的相关性。这些结果表明，AcrAB-TolC外排泵过表达与高水平的氟喹诺酮耐药和选择具有增强的氟喹诺酮耐药的菌株有关。
Fluoroquinolone resistance is mainly caused by mutations in quinolone resistance-determining regions of DNA gyrase and topoisomerase IV in Escherichia coli. The AcrAB-TolC efflux pump contributes to resistance against fluoroquinolone and other antimicrobials. In this study, we investigated a high-level mechanism of fluoroquinolone resistance in E. coli that was isolated from human clinical samples and canine fecal samples. E. coli strains with high levels of fluoroquinolone resistance have been found to be frequently resistant to cephalosporins. Strains with high-level fluoroquinolone resistance exhibited lower intracellular enrofloxacin (ENR) concentrations, higher expression of AcrA, and a greater reduction in the fluoroquinolone minimum inhibitory concentration for treatment with an efflux pump inhibitor. The frequency of strains with enhanced ENR resistance selection and the survival rate of E. coli in the presence of ENR in vitro were correlated well with AcrA protein expression levels in the parental strains. These results suggest that AcrAB-TolC efflux pump over-expression is related to high-level fluoroquinolone resistance and the selection of strains with enhanced fluoroquinolone resistance.