Analysis of mechanisms of resistance and tolerance of Escherichia coli to enrofloxacin
Analysis of mechanisms of resistance and tolerance of Escherichia coli to enrofloxacin
复制标题
大肠杆菌对恩诺沙星的耐药和耐受机制分析
DOI：
10.1007/s13213-011-0260-3
复制
发表时间：
2012-03-01
影响因子：
3
通讯作者：
Liu, Yu-qing
中科院分区：
文献类型：
--
作者：
Bai, Hua;Du, Jia-fa;Liu, Yu-qing
研究了降低细菌对药物敏感性的机制以及这种现象的本质。用亚抑菌剂量或重复加倍剂量的恩诺沙星（EN）体外处理大肠杆菌。连续传代10次后，通过SOS反应、药物外排泵、孔蛋白和EN靶基因表达的变化以及喹诺酮类药物耐药决定区（QRDR）的突变来评估EN对细菌的最小抑菌浓度（MIC）。结果表明，EN对大肠杆菌的MIC为1.05，对大肠杆菌的MIC为1.05。与对照组（0.5 μg/ml）相比，用两种浓度的EN处理的大肠杆菌在单次传代后的细胞数均较高。从这一点出发，E.亚抑菌浓度处理后，大肠杆菌的抑菌活性趋于稳定，而倍增浓度处理后，大肠杆菌的抑菌活性继续上升，达到64 μg/ml。无论细菌暴露于何种EN浓度，它们的外排泵都被启动，SOS调节基因recA和umuC以及EN靶基因parC的表达显著上调，而孔蛋白基因ompW的表达显著下调。在E.用亚抑菌浓度的EN处理大肠杆菌，但在三个位点上的突变发生在重复加倍剂量处理后。 急诊大肠杆菌对恩诺沙星胁迫的适应机制包括SOS反应、靶基因突变和外排泵活性等，这些适应机制是相互作用的，但遗传和非遗传机制在细菌对药物的适应中发挥着不同的作用。
The mechanisms behind reduced bacterial sensitivity to drugs and the nature of this phenomenon were explored. Escherichia coli were treated with a sub-inhibitory dose or a repeatedly doubled dose of enrofloxacin (EN) in vitro. After 10 serial passages, the minimal inhibitory concentration (MIC) of EN to the bacteria was assessed by changes in expression of genes involved in the SOS response, drug efflux pumps, porins and EN targets, and the mutation of the quinolone resistance determining region (QRDR). The results showed that the MIC of EN to E. coli was higher after a single passage when treated with either concentration of EN compared with that of the controls (0.5 μg/ml). From this point onwards, the MIC of E. coli treated with the sub-inhibitory concentration tended to be stable, whilst it increased continuously to 64 μg/ml when treated with the doubling dose. Regardless of the EN concentration that bacteria were exposed to, their efflux pumps were started, the expression of the SOS regulatory genes recA and umuC and EN target gene parC were significantly up-regulated, and the expression of the porins gene ompW was significantly down-regulated. No mutations were detected in the QRDR of E. coli treated with the sub-inhibitory concentration of EN, but mutations at three sites occurred after treatment with the repeatedly doubling dose. The E. coli studied initiated mechanisms to adapt to the enrofloxacin stress which included an SOS response, target gene mutations and efflux pump activity and so on. These adaptive mechanisms are interactive, but the inherited and non-inherited mechanisms play different roles in the adaptation of bacteria to drugs.