文章摘要

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

作者: 1,2王华, 3宿俊彪, 4庞丹, 2胡志德, 2王俊瑞, 1,2郑文琪
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
通讯: 王俊瑞 Email: wangjunrui123@yeah.net
郑文琪 Email: zhengwenqi2011@163.com
DOI: 10.3978/j.issn.2095-6959.2022.06.002
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(Enterobacter cloacae,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(carbapenem-resistant Enterobacter cloacae,CRECL),分别命名为FY-1和Y-2,采用VITEK-2 Compact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/ionisation time-of-flight mass spectrometry,MALDI-TOF MS)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。FY-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fosAACT-7TEM-1BblaIMP-1,及外排泵系统相关基因mdf(A)。Y-2携带耐药基因fosAACT-16aac(6’)-Ib-crCTX-M-3、TEM-1B与blaIMP-8,及外排泵相关基因OqxAOqxBmdf(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blaIMP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CRECL具有密切的亲缘关系。结论:CRECL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。
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

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

Authors: 1,2WANG Hua, 3SU Junbiao, 4PANG Dan, 2HU Zhide, 2WANG Junrui, 1,2ZHENG Wenqi
1 Department of Parasitology, College of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010050, China
2 Department of Laboratory Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
3 Department of Laboratory Medicine, Inner Mongolia People’s Hospital, Hohhot 010020, China
4 Department of Laboratory Medicine, Inner Mongolia Women and Children’s Hospital, Hohhot 010020, China

CorrespondingAuthor: WANG Junrui Email: wangjunrui123@yeah.net

DOI: 10.3978/j.issn.2095-6959.2022.06.002

Foundation: This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region (2020MS08126), the 2020 “Grassland Talents” Project Youth Innovation and Entrepreneurship Talent Training Program of Inner Mongolia, and the General Foundation of Inner Mongolia Medical University (YKD2021MS011), China.

Abstract

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 resistance-related 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-1B and blaIMP-1, 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-1B and blaIMP-8, and efflux pump system-related 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 ST175 and ST114, 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.

Keywords: carbapenem-resistant Enterobacter cloacae; whole-genome sequencing; multi-site sequence typing; IMP carbapenemase

文章选项