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摘要
The mechanisms behind reduced bacterial sensitivity to drugs and the nature of this phenomenon were explored. Escherichia coli were treated with a subinhibitory 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 mu g/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 mu g/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 current results suggest that the reduction in sensitivity of bacteria to drugs is positively, but non-linearly, correlated with the concentration of drugs used. 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.
- 出版日期2012-3
- 单位山东省农业科学院
