31株深圳地区婴幼儿感染百日咳鲍特菌的流行特点、基因型、亲缘关系与大环内酯耐药性  

Epidemiological characteristics,genotypes,genetic relationships and macrolide resistance of 31 Bordetella pertussis strains isolated from infants and young children in Shenzhen

作　　者：姜含芳 刘孝荣[1] 陈虹宇[1] 朱纯青 邢志浩 马东礼[1] Jiang Hanfang;Liu Xiaorong;Chen Hongyu;Zhu Chunqing;Xing Zhihao;Ma Dongli(Shenzhen Engineering Laboratory for High-throughput Gene Sequencing of Pathogens,Shenzhen Children′s Hospital,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院深圳病原体高通量基因测序技术工程实验室,518038

出　　处：《中华微生物学和免疫学杂志》2019年第4期270-276,共7页Chinese Journal of Microbiology and Immunology

基　　金：深圳市科创委基础研究项目(JCYJ20160429181145972,JCYJ20170413094034978);深圳市卫计委临床研究课题(SZLY2017016).

摘　　要：目的通过分析百日咳感染患儿的临床信息和鉴定百日咳鲍特菌的基因型、耐药性和亲缘性,了解深圳地区百日咳鲍特菌的流行特点、基因组变异与大环内酯类耐药情况。方法百日咳患儿的临床信息采集自深圳市儿童医院电子病历系统。我们对分离自患儿咽拭子的31株百日咳鲍特菌进行二代测序和基因组从头组装。通过序列比对鉴定多位点序列分型(multilocus sequence typing,MLST)、毒力基因型与23S rRNA突变位点。通过构建系统进化树分析亲缘性。通过E-test鉴定临床分离株对大环内酯类抗生素的耐药性。结果31株百日咳鲍特菌的MLST分型均为ST-2。毒力基因型呈多样性,其中2株为prn缺失型。基于进化树,深圳株与疫苗株亲缘关系远。19株百日咳鲍特菌为红霉素耐药,均携带23S rRNA编码基因的A2047G突变。结论深圳地区百日咳鲍特菌的毒力基因型呈多样性,非疫苗株的基因型逐渐增多。大环内酯耐药株已有传播。本研究为改进百日咳的防治和疫苗策略提供了参考。Objective To understand the epidemiological characteristics,genomic variations and macrolide resistance of Bordetella pertussis(B.pertussis)strains circulating in Shenzhen with clinical data analysis,genotype profiling,phylogenetic analysis and antimicrobial susceptibility test.Methods Clinical data of patients with pertussis in Shenzhen Children′s Hospital were collected from the electronic medical record system.Genome sequences of 31 B.pertussis isolates were analyzed with next-generation sequencing and de novo assembled.Multilocus sequence typing(MLST)was performed to identify their sequences types.Sequence alignment by BLASTn was used to identify virulence genotypes and mutations in 23S rRNA gene.A phylogenetic tree was constructed to analyze the relationships among them.E-test was used to identify macrolide resistance.Results All of the 31 B.pertussis strains were identified as sequence type-2(ST-2)by MLST with diverse virulence genotypes.Two were prn-deficient strains.Based on the phylogenetic tree,all of the isolates were distant from vaccine strains.Nineteen isolates were resistant to erythromycin with A2047G mutation in 23S rRNA.Conclusions The virulence genotypes of B.pertussis strains in Shenzhen were diverse with increasing non-vaccine genotypes.Macrolide-resistant strains were prevalent.This study might provide reference for improving the prevention,management and vaccination strategy of pertussis.

关 键 词：百日咳鲍特菌 二代测序 基因型 大环内酯耐药性 

分 类 号：R725.1[医药卫生—儿科] R446.5[医药卫生—临床医学]