2株产IMP型碳青霉烯酶阴沟肠杆菌的耐药特点及全基因组测序分析  

Characteristics of drug resistance and whole-genome sequencing of two IMP carbapenemase-producing Enterobacter cloacae strains

作　　者：王华 宿俊彪[3] 庞丹 胡志德 王俊瑞 郑文琪[1,2] WANG Hua;SU Junbiao;PANG Dan;HU Zhide;WANG Junrui;ZHENG Wenqi(Department of Parasitology,College of Basic Medical Sciences,Inner Mongolia Medical University,Hohhot 010050;Department of Laboratory Medicine,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050;Department of Laboratory Medicine,Inner Mongolia People’s Hospital,Hohhot 010020;Department of Laboratory Medicine,Inner Mongolia Women and Children’s Hospital,Hohhot 010020,China)

机构地区：[1]内蒙古医科大学基础医学院寄生虫学教研室,呼和浩特010050 [2]内蒙古医科大学附属医院检验科,呼和浩特010050 [3]内蒙古自治区人民医院检验科,呼和浩特010020 [4]内蒙古自治区妇幼保健院检验科,呼和浩特010020

出　　处：《临床与病理杂志》2022年第6期1275-1283,共9页Journal of Clinical and Pathological Research

基　　金：内蒙古自治区自然科学基金面上项目(2020MS08126);2020年度内蒙古自治区“草原英才”工程青年创新创业人才培养计划;2021年度内蒙古医科大学校级面上项目(YKD2021MS011)。

摘　　要：目的:了解产IMP型碳青霉烯酶阴沟肠杆菌(Enterobactercloacae,ECL)的耐药性及分子遗传特点,为其抗感染防控及相关深入研究提供理论依据。方法:收集2017年7月至2021年5月内蒙古自治区呼和浩特市两家三级医院分离的2株IMP阳性耐碳青霉烯类阴沟肠杆菌(carbapenemresi stantEnterobac tercloacae,CR ECL),分别命名为F Y-1和Y-2,采用VITEK-2Compact全自微生物鉴定药敏分析仪和基质辅助激光解吸电离-飞行时间质谱仪(matrix-assisted laser desorption/ionisationtime-of-flightmassspectrometr y,MALDI-TOFMS)进行菌种鉴定及复核。应用琼脂稀释法进行药敏试验。采用全基因组测序技术进行耐药相关分子、质粒同源性及全基因组遗传进化分析。结果:FY-1对头孢他啶/阿维巴坦、磷霉素和大部分β-内酰胺类抗生素均耐药,对多黏菌素B表现为中介,仅对妥布霉素、庆大霉素、环丙沙星、氯霉素、氨曲南和阿米卡星敏感。Y-2对除多黏菌素B、磷霉素和阿米卡星外的其他抗生素均表现为耐药。F Y-1和Y-2均含有1条染色体和3个环状质粒。FY-1含有耐药基因fos A、ACT-7、TEM-1B与blaI M P-1,及外排泵系统相关基因mdf(A)。Y-2携带耐药基因fos A、ACT-16、aac(6’)-Ib-cr、CTX-M-3、TEM-1B与blaI MP-8,及外排泵相关基因OqxA、OqxB和mdf(A)。FY-1和Y-2的IMP型碳青霉烯酶亚型分别为IMP-1和IMP-8,两者的blaI M P基因均位于质粒上,且2个质粒高度同源。FY-1和Y-2序列型分别为ST175和ST114,全基因组同源性分析提示菌株FY-1和Y-2的亲缘关系较近,两者分别与捷克共和国和荷兰分离的CR ECL具有密切的亲缘关系。结论:CR ECL的耐药形势严峻且菌株间的遗传关系密切,应加强泛耐药CRECL的耐药监测及相关分子生物学研究。Objective:To understand the drug resistance profile and genetic characteristics of IMP-producing Enterobacter cloacae strains.Methods:Two IMP-producing carbapenem-resistant Enterobacter cloacae(CRECL) were isolated from Hohhot from July 2017 to June 2021,termed FY-1 and Y-2,respectively.Species identification was performed using the VITEK-2 compact system and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry(MALDI-TOF MS).Antimicrobial susceptibility testing was performed using the standard agar microdilution method.Whole-genome sequencing technology was applied to analyze the characteristics of drug resistancerelated molecular,plasmid homology and genetic evolution.Results:FY-1 was resistant to ceftazidime/avibactam,fosfomycin and most of the β-lactam antibiotics.While intermediate to polymyxins B,and sensitive to tobramycin,gentamicin,ciprofloxacin,chloramphenicol,aztreonam and amikacin.Y-2 was resistant to all antibiotics tested except for polymyxin B,fosfomycin and amikacin.Both FY-1 and Y-2 contain one chromosome and three circular plasmids.FY-1 carried drug resistance genes fosA,ACT-7,TEM-1 B and bla;, and efflux pump system-related gene mdf(A).Y-2 carried drug-resistant genes fosA,ACT-16,aac(6’)-Ib-cr,CTX-M-3,TEM-1 B and bla;,and efflux pump systemrelated genes OqxA,OqxB and mdf(A).The IMP subtypes of FY-1 and Y-2 were IMP-1 and IMP-8,respectively,and both of them were located on plasmids.These two plasmids were highly homologous.The sequences of FY-1 and Y-2 were ST 175 and ST 114,respectively.Homology analysis suggested that strains FY-1 and Y-2 were closely related to the CRECL strains isolated from Czech Republic and Netherlands.Conclusion:The antimicrobial resistance of IMP-producing CRECL strains is severe,and their genetic relationship is high in homology.Antimicrobial resistance and molecular biology research of CRECL should be monitored in clinical.

关 键 词：耐碳青霉烯类阴沟肠杆菌 全基因组测序 多位点序列分型 IMP型碳青霉烯酶 

分 类 号：R446.5[医药卫生—诊断学]