Enhanced expression of the multidrug efflux pumps AcrAB and AcrEF associated with insertion element transposition in Escherichia coli mutants selected with a fluoroquinolone
Enhanced expression of the multidrug efflux pumps AcrAB and AcrEF associated with insertion element transposition in Escherichia coli mutants selected with a fluoroquinolone
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DOI：
10.1128/aac.45.5.1467-1472.2001
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发表时间：
2001-05-01
影响因子：
4.9
通讯作者：
Kern, WV
中科院分区：
文献类型：
--
作者：
Jellen-Ritter, AS;Kern, WV
大肠埃希菌对氟喹诺酮类药物耐药的发生可能与其调控基因位点如marRAB的突变有关，这些突变可能通过激活AcrAB多药外排泵的表达而导致多药外排增加。大肠杆菌K-12菌株中gyrA基因的喹诺酮类耐药决定区发生单突变，经两步筛选后从mar基因敲除菌株中获得突变株3-AG 100 MKX，其acrB的表达在逆转录酶PCR中增强，与AcrA 8阻遏基因acrR中插入IS 186有关。在这些突变体中增强的外排是由于acrEF的表达增加，并与插入到acrEF的上游区域的IS2，大概创建一个混合启动子。这些观察结果证实了外排相关的非靶基因突变的重要性，并表明遗传元件的转座可能在大肠埃希菌氟喹诺酮耐药的发展中起作用。杆菌
The development of fluoroquinolone resistance in Escherichia coli may be associated with mutations in regulatory gene loci such as marRAB that lead to increased multidrug efflux, presumably through activation of expression of the AcrAB multidrug efflux pump, We found that multidrug-resistant (MDR) phenotypes with enhanced efflux can also be selected by fluoroquinolones from marRAB- or acrAB-inactivated E. coli K-12 strains having a single mutation in the quinolone-resistance-determining region of gyrA, Mutant 3-AG100MKX, obtained from a mar knockout strain after two selection steps, showed enhanced expression of acrB in a reverse transcriptase PCR associated with insertion of IS186 into the AcrA8 repressor gene acrR, In vitro selection experiments with acrAB knockout strains yielded MDR mutants after a single step. Enhanced efflux in these mutants was due to increased expression of acrEF and associated with insertion of IS2 into the upstream region of acrEF, presumably creating a hybrid promoter. These observations confirm the importance of efflux-associated nontarget gene mutations and indicate that transposition of genetic elements may have a role in the development of fluoroquinolone resistance in E. coli.