小肠结肠炎耶尔森菌O:3血清型喹诺酮耐药的分子机制研究  

Molecular mechanism of resistance to quinolone in clinical Yersinia enterocolitica O:3 isolates

作　　者：王连明[1] 于鸿[2] 杨超[3] 路娟[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院实验诊断教研室,黑龙江哈尔滨150001 [2]广州市疾病预防控制中心,广东广州510080 [3]哈尔滨市疾病预防控制中心,黑龙江哈尔滨150056

出　　处：《哈尔滨医科大学学报》2009年第6期580-583,共4页Journal of Harbin Medical University

基　　金：黑龙江省自然科学基金(D0210);黑龙江省卫生厅立项资助(2002-025)

摘　　要：目的研究中国部分地区小肠结肠炎耶尔森菌菌株的耐药特征,为小肠结肠炎耶尔森菌感染的预防控制工作提供依据。方法自2002年至2007年,选择几个省市在不同季节对腹泻人群进行了该病原菌的分离,并对分离到的菌株进行血清学分型、生物学分型、药敏试验以及gyrA和parC基因突变检测。结果通过对该菌喹诺酮耐药决定区gyrA和parC基因的变异情况检测发现,在22株萘啶酸耐药的菌株中,有20株gyrA基因检出氨基酸变异,其中83位点共检出Ser(AGC)→Arg(AGA或AGG)突变12株,Ile(ATC)突变3株,Cys(TGC)1株,87位点检出Gly(GGC)突变2株,Tyr(TAC)和Asn(AAC)突变各1株;3株萘啶酸敏感O∶3血清型小肠结肠炎耶尔森菌未检出上述氨基酸位点突变,而parC基因无论耐药株或敏感株均未检出突变。结论我国小肠结肠炎耶尔森菌对萘啶酸的耐药比较严重,这可能是因为氟喹诺酮类抗生素是临床最常用药物之一,而高水平用药,用药时间过长,以及动物饲料中抗生素的使用可能是小肠结肠炎耶尔森菌对喹诺酮类抗生素耐药的根本原因。氟喹诺酮的过度应用使萘啶酸耐药株选择性形成。Objective To investigate the antimicrobial susceptibility of Y. enterocolitica isolates to quinolones and other antibiotics,and to explore the quinolone resistance determining region （QRDR） mutations in nalidixic acid-resistant Y. enterocolitica. Methods Susceptibility tests were performed for 22 Y. enterocolitica isolates collected from 4 provinces during 2002 ～ 2007 using an agar dilution method according to the NCCLS guidelines. Selected Nalidixic acid-resistant Y. enterocolitica were analyzed by sequencing to understand the mutations in QRDR, including gyrA and parC genes. Results There were mutations at gyrA genes among 20 of the 22 clinical Y. enterocoliticn, affecting the amino acid eodons Set-83 or Asp-87.12 showed gyrA： Ser（ AGC）83→Arg（ AGA or AGG）, and some strains had additional substitution ofgyrA： Ser（AGC）83→Ule（ATC） or Cys（TGC）, Asp （GAC）87→Gly（GGC）, Tyr（TAC） or Asn（AAC）. None of the isolates showed amino acid substitution in parC genes. Conclusion Y. enterocolitica strains which have acquired different mutations at the quinolone resistance determining region can generate resistance to nalidixic acid and which has probably emerged due to the selective pressure exerted by the overuse of fluoroquinolones.

关 键 词：小肠结肠炎耶尔森菌 萘啶酸 喹诺酮耐药决定区 

分 类 号：R574[医药卫生—消化系统]