首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >In Vitro Selection of ramR and soxR Mutants Overexpressing Efflux Systems by Fluoroquinolones as Well as Cefoxitin in Klebsiella pneumoniae
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In Vitro Selection of ramR and soxR Mutants Overexpressing Efflux Systems by Fluoroquinolones as Well as Cefoxitin in Klebsiella pneumoniae

机译:氟喹诺酮类和头孢西丁在肺炎克雷伯菌中体外筛选ramR和soxR突变体外排系统

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摘要

The relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported in Klebsiella pneumoniae. In 3 previously published clinical isolates and 17 in vitro mutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR, ramR, ramA, marR, marA, soxR, soxS, and rob) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressed acrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in the ramR gene in 8 of them and in the soxR gene in the last one, resulting in overexpression of ramA and soxS, respectively. Transformation of the ramR mutants and the soxR mutant with the wild-type ramR and soxR genes, respectively, abolished overexpression of acrB and ramA in the ramR mutants and of soxS in the soxR mutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that the ramR and soxR genes control the expression of efflux systems in K. pneumoniae and suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression.
机译:最近在肺炎克雷伯菌中报道了外排系统过表达与对头孢西丁,喹诺酮和氯霉素的交叉耐药性之间的关系。在3种先前发表的临床分离株和用头孢西丁或氟喹诺酮类药物选择的17种体外突变体中,搜索了AcrAB外排泵潜在调节因子基因的突变(acrR,ramR,ramA,marR,marA,soxR,soxS和rob)评估了它们对与流出相关的抗生素交叉耐药性的影响。除1和2个临床分离株外,所有突变体均过表达acrB。在临床分离株和8个突变体中研究的调节基因中未检测到突变。对于剩下的9个突变体,在其中8个突变体的ramR基因和最后一个突变体的soxR基因中发现了一个突变,分别导致ramA和soxS的过表达。用野生型 ramR soxR 基因分别转化ramR突变体和 soxR 突变体,从而消除了 acrB < / em>和 ramA ramR 突变体中和 soxS soxR 突变体中,以及抗生素交叉-抵抗性。四种新抗生素证明了由于外排系统过表达引起的耐药性:头孢呋辛,头孢噻肟,头孢他啶和厄他培南。这项研究表明 ramR soxR 基因控制 K中外排系统的表达。肺炎,提示存在除AcrAB以外的外排泵和参与调节AcrAB表达的其他基因座。

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