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评估铜绿假单胞菌多重耐药临床分离株中氟喹诺酮类药物耐药机制。

Evaluation of fluoroquinolone resistance mechanisms in Pseudomonas aeruginosa multidrug resistance clinical isolates.

机构信息

Department of Genetics and Microbiology, University of Pavia, Pavia, Italy.

出版信息

Microb Drug Resist. 2012 Feb;18(1):23-32. doi: 10.1089/mdr.2011.0019. Epub 2011 Jul 28.

Abstract

Efflux transporters have a considerable role in the multidrug resistance (MDR) of Pseudomonas aeruginosa, an important nosocomial pathogen. In this study, 45 P. aeruginosa clinical strains, with an MDR phenotype, have been isolated in a hospital of Northern Italy and characterized to identify the mechanisms responsible for their fluoroquinolone (FQ) resistance. These isolates were analyzed for clonal similarity, mutations in genes encoding the FQ targets, overexpression of specific Resistance Nodulation-cell Division efflux pumps, and search for mutations in their regulatory genes. The achieved results suggested that the mutations in genes encoding ciprofloxacin targets represented the main mechanism of FQ resistance of these strains; 97.8% of these isolates showed mutations in gyrA, 28.9% in gyrB, 88.9% in parC, and 6.7% in parE. Another mechanism of resistance was overexpression of the efflux pumps in some representative strains. In particular, overexpression of MexXY-OprM drug transporter was found in five isolates, whereas overexpression of MexCD-OprJ was detected in two isolates; surprisingly, in one of these last two isolates, also overexpression of MexAB-OprM pump was identified.

摘要

外排转运蛋白在铜绿假单胞菌(一种重要的医院病原体)的多药耐药(MDR)中起着重要作用。在这项研究中,在意大利北部的一家医院中分离出了 45 株具有 MDR 表型的铜绿假单胞菌临床株,并对其进行了特征分析,以确定导致其氟喹诺酮(FQ)耐药的机制。这些分离株的克隆相似性、编码 FQ 靶标的基因突变、特定耐药结节分裂外排泵的过度表达以及其调节基因的突变情况进行了分析。研究结果表明,编码环丙沙星靶标的基因突变是这些菌株 FQ 耐药的主要机制;这些分离株中有 97.8%显示出在 gyrA 基因、28.9%在 gyrB 基因、88.9%在 parC 基因和 6.7%在 parE 基因的突变。在一些代表性菌株中,外排泵的过度表达也是一种耐药机制。特别是,在 5 株分离株中发现了 MexXY-OprM 药物转运蛋白的过度表达,而在 2 株分离株中检测到了 MexCD-OprJ 的过度表达;令人惊讶的是,在这两个分离株中的一个中,还鉴定出了 MexAB-OprM 泵的过度表达。

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