高毒力肺炎克雷伯菌携带质粒泛基因组分析  

Pangenome analysis on plasmids carried by hypervirulent Klebsiella pneumoniae

作　　者：吴鑫淼 李臻鹏 黄佳[3] 王瑜昊 卢昕[2] 阚飙[2] 赵俊岭[1] Wu Xinmiao;Li Zhenpeng;Huang Jia;Wang Yuhao;Lu Xin;Kan Biao;Zhao Junling(School of Public Health,Xinjiang Medical University,Urumqi 830011,China;National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases,National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;The Pathogenic Organism Examination Institute,Xinjiang Uyghur Autonomous Region Center for Disease Control and Prevention,Urumqi 830002,China)

机构地区：[1]新疆医科大学公共卫生学院,乌鲁木齐830011 [2]传染病溯源预警与智能决策全国重点实验室,中国疾病预防控制中心传染病预防控制所,北京102206 [3]新疆维吾尔自治区疾病预防控制中心病原生物检定所,乌鲁木齐830002

出　　处：《中华流行病学杂志》2025年第3期506-513,共8页Chinese Journal of Epidemiology

基　　金：国家重点研发计划(2022YFC2303900)。

摘　　要：目的以全球高毒力肺炎克雷伯菌(hvKP)携带的质粒为研究对象,从质粒泛基因组、泛耐药基因、泛毒力基因及泛复制子等多个方面分析其特征及随时间演化趋势,从而为理解质粒遗传多样性、耐药基因、毒力基因等演化提供更全面的认识。方法从美国国家生物技术信息中心数据库2136株携带质粒的hvKP基因组完成图中筛选出524株菌株携带的1738个高毒力质粒,通过分析泛基因组、泛耐药基因、泛毒力基因等构成及功能,绘制泛基因组、新基因大小随质粒分离时间增长曲线,揭示质粒泛基因组的多样性及演化规律。结果hvKP携带质粒的同源基因、同源耐药基因、同源毒力基因及复制子分别为12906、149、107和89个。新基因、新耐药基因及新复制子数目随质粒数目增加的拟合曲线呈现开放状态,而新毒力基因呈闭合状态。新耐药基因在2018-2019年出现明显增加,2021-2023年新增耐药基因中除了对氨基糖苷类耐药的基因外,主要为碳青霉烯类耐药的新亚型基因。结论hvKP携带质粒的泛基因组具有高度多样性,质粒泛基因、泛耐药基因、泛复制子类型呈逐渐增加状态,而泛毒力基因呈稳定状态;新耐药基因在特定年份的增加及2021-2023年碳青霉烯类新耐药基因亚型的出现提示应加强耐药监测和防控工作,并特别关注碳青霉烯类抗生素的耐药。Objective To analyze the pangenome,pan drug resistance genes,pan virulence genes,pan replicons,and others of the plasmids carried by hypervirulent Klebsiella pneumoniae(hvKP)in the world and their evolutionary trends over time,and provide evidence for more comprehensive understanding of the evolution of genetic diversity,drug resistance genes,and virulence genes of the plasmids.Methods From the National Center for Biotechnology Information database,a total 1738 plasmids were screened from 524 strains with completed genome sequences in 2136 strains of hvKP carrying plasmids.Through pangenome,pan drug resistance gene,and pan-virulence gene composition and functional analyses,the curves of pangenome size and new gene size against plasmid isolation time were established,revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results The homologous genes,homologous drug resistance genes,homologous virulence genes,and replicons of the plasmids carried by hvKP comprised of 12906,149,107 and 89 types,respectively.The fitting curves for the number of new genes,new drug resistance genes and new replicons increased with the increase of plasmids in an open state,while the curve for novel virulence genes was in a closed state.A obvious increase in new drug resistance genes was observed during 2018-2019.Among the newly added drug resistance genes during 2021-2023,beside those conferring aminoglycoside resistance,they were mainly new subtypes conferring carbapenem resistance.Conclusions The pangenome of plasmids carried by hvKP exhibited high diversity,with the plasmid pan genes,pan drug resistance genes,and pan replicon types gradually expanding,while the pan virulence genes remains stable.The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts,with particular attention to carbapenem resistance.

关 键 词：肺炎克雷伯菌 泛基因组 耐药基因 毒力基因 复制子 

分 类 号：R73[医药卫生—肿瘤]