多重耐药肺炎克雷伯菌发现一组gyrA,parC,qnrS基因新变异型

朱健铭; 姜如金; 孔海深; 张嵘; 吕火祥; 孙长贵; 黄支密

Abstract

朱健铭,姜如金,孔海深,张嵘,吕火祥,孙长贵,黄支密.多重耐药肺炎克雷伯菌发现一组gyrA,parC,qnrS基因新变异型[J].Chinese journal of Epidemiology,2013,34(1):61-66

多重耐药肺炎克雷伯菌发现一组gyrA,parC,qnrS基因新变异型

Emergence of novel variants of gyrA, parC, qnrS genes in mufti-drug resistant Klebsiella caused pneumonia

Received:September 13, 2012

DOI：10.3760/cma.j.issn.0254-6450.2013.01.016

KeyWord: 肺炎克雷伯菌唆诺酮类新变异型喳诺酮耐药决定区多重耐药

English Key Word: Klebsiella pnenmoniae Quinolone Novel variant Quinolone-resistance-determining region Multi-drug resistance

FundProject:国家自然科学基金(81001267/H2609);北京市科技新星项目(2010B067)

Author Name	Affiliation	E-mail
Zhu Jian-ming	Department of Microbiology Laboratory, Yuhang Hospital of Traditional Chinese Medicine311106, China	zhujiamning001@126.com
Jiang Ru-jin	Department of Microbiology Laboratory, Yuhang Hospital of Traditional Chinese Medicine311106, China
Kong Hai-shen	Medical Laboratory Department of the First Affiliated Hospital
Zhang Rong	Medical Laboratory Department of the Second Affiliated Hospital,fang University
Lv Huo-xiang	The Center of Medical Laboratory, Zhejiang Provincial People of Medicines Hospital
Sun Chang-gui	Department of Medical Laboratory, the No. 117 Hospital of PLA
Huang Zhi-mi	Department of Medical Laboratory,the No. 98 Hospital of PLA

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Abstract:

目的研究多重耐药肺炎克雷伯菌(MDR-KPN)对喳诺酮类药物的耐药机制。方法收集2008年8月至2010年5月浙江省杭州市和湖州市6所医院共47株MDR-KPN，采用聚合酶链反应((PCR)及序列分析方法分析喳诺酮类药物作用靶位编码基因gyrA,parC和可移动遗传元件介导的喳诺酮类耐药基因[qnrA,qnrB,qnrS,aac(6')-I b-cr, qepA ]。结果47株MDR-KPN中检出43株(91.5% gyrA突变、40株(85.1 % ) parC突变、3株(6.4% ) qnrB2,1株(2.1%)qnrB4,8株(17.0%)qnrS1,5株(10.6% ) qnrS4, 2株(4.3% ) aac (6')-I b-cr，发现5株gyrA基因新的变异型( GenBank登录:JN811952,JN811953,JN811954,JN811955,JN811956),5株parC基因新的变异型(GenBank登录:JN817432,JN817433,IN817434,JN817435,JN817436),qnrS4为首次发现的qnrS变异型(GenBank登录号:JN836269)。结论本组菌株喳诺酮类药物耐药主要与gyrA和parC基因的喳诺酮耐药决定区(QRDR )有义突变相关，部分菌株可检出qnrB2,qnrB4,qnrS1,qnrS4,aac(6')-I b-cr等可移动遗传元件介导的哇诺酮类耐药基因。检出qnrS4为国内外首次报道。

English Abstract:

Objective To investigate the resistant mechanism of quinolones on multi-drug resistant Klebsiella caused pneumonia(MDR-ICPN).Methods From August 2008 to May 2010, 47strains of MDR-ICPN were collected from 6 hospitals in Hangzhou and Huzhou in Zhejiang province in China. Drug target genes to quinolones (gyrA, parC) and quinolone-resistance genes mediated by mobile genetic elements [qnrA, qnrB, qnrS, aac (6')-I b-cr, qepA] were analyzed by PCR and verified by DNA sequencing. Results Positive Results were found in 47 strains of MDR-KPN，43 strains ( 91.5% ) of gyrA mutation, 40 strains ( 85.1 % ) of parC mutation, 3 strains ( 6.4% ) of qnrB2,1 strain ( 2.1 % ) of qnrB 4, 8 strains(17.0% ) of qnrS 1, 5 strains(10.6% ) of qnrS 4, 2 strains ( 4.3 % )of aac ( 6')-I b-cr respectively. Moreover, 5 novel variants of gyrA (GenBank accession number: JN811952, JN811953> JN811954, IN811955，JN811956)，S novel variants of parC (GenBank accession number:IN817432, JN817433，JN817434,JN817435，JN817436) were also identified. In addition, qnrS4 (GenBank accession number: JN836269) appeared to be the novel variants of qnrS.Conclusion Quinolone-resistance-determining region played a key role on the resistance to quinolones in this group of MDR-ICPN, and quinolone-resistance genes mediated by mobile genetic elements [ qnrB2, qnrB4, qnrS 1，qnrS4, aac(6')-I b-cr] showed positive in some parts of the strains. This was the first report on emergence of qnrS4 in the world

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