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耐碳青霉烯类铜绿假单胞菌毒力基因型与氟喹诺酮耐药性之间的相关性

Correlation between virulence genotype and fluoroquinolone resistance in carbapenem-resistant Pseudomonas aeruginosa.

作者信息

Cho Hye Hyun, Kwon Kye Chul, Kim Semi, Koo Sun Hoe

机构信息

Department of Biomedical Laboratory Science, Jeonju Kijeon College, Jeonju, Korea.

Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.

出版信息

Ann Lab Med. 2014 Jul;34(4):286-92. doi: 10.3343/alm.2014.34.4.286. Epub 2014 Jun 19.

DOI:10.3343/alm.2014.34.4.286
PMID:24982833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4071185/
Abstract

BACKGROUND

Pseudomonas aeruginosa is a clinically important pathogen that causes opportunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa. ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype (exoS and exoU), fluoroquinolone resistance, and target site mutations in 66 carbapenem-resistant P. aeruginosa strains.

METHODS

Sixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE.

RESULTS

A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P≤0.0001). Additionally, exoU+ strains were more likely to carry combined mutations than exoS+ strains (97.6%, 40/41 vs. 70%, 7/10; P=0.021), and MIC increased as the number of active mutations increased.

CONCLUSIONS

The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa. These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance-conferring mutations.

摘要

背景

铜绿假单胞菌是一种临床上重要的病原体,可引起机会性感染和医院感染暴发。最近,Ⅲ型分泌系统(TTSS)已被证明在铜绿假单胞菌的毒力中起重要作用。特别是ExoU,对疾病严重程度影响最大。我们研究了66株耐碳青霉烯类铜绿假单胞菌菌株中TTSS效应子基因型(exoS和exoU)、氟喹诺酮耐药性和靶位点突变之间的关系。

方法

2008年1月至2012年5月,从韩国大田一家大学医院的患者中收集了66株耐碳青霉烯类铜绿假单胞菌菌株。采用琼脂稀释法测定氟喹诺酮类药物(环丙沙星和左氧氟沙星)的最低抑菌浓度(MIC)。我们使用聚合酶链反应(PCR)和测序来确定TTSS效应子基因型以及各自靶基因gyrA、gyrB、parC和parE的喹诺酮耐药决定区(QRDR)。

结果

exoU+菌株对氟喹诺酮耐药的比例高于exoS+菌株(93.2%,41/44对45.0%,9/20;P≤0.0001)。此外,exoU+菌株比exoS+菌株更有可能携带联合突变(97.6%,40/41对70%,7/10;P=0.021),并且MIC随着活性突变数量的增加而增加。

结论

近期氟喹诺酮的过度使用导致耐碳青霉烯类铜绿假单胞菌的耐药性增加和毒力增强。这些数据表明exoU基因型、氟喹诺酮耐药性和耐药性赋予突变之间存在特定关系。

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