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高毒力碳青霉烯耐药肺炎克雷伯菌的院内播散与分子进化

Chasing the landscape for intrahospital transmission and evolution of hypervirulent carbapenem-resistant Klebsiella pneumoniae
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摘要 高毒力碳青霉烯耐药肺炎克雷伯菌(Hv-CRKP)已成为全球公共卫生领域的重大挑战.该研究报告了2017年至2022年浙江一家三甲医院Hv-CRKP分离株的定植和传播情况.对来自72名患者的90个不同的CRKP菌株进行测序分析,发现院内感染Hv-CRKP的流行主要依赖于ST11-K64克隆传播.对11个代表性分离株进行了全基因组测序,得到了31个完整的质粒基因序列,其中包括12个携带KPC-2耐药基因的质粒和10个携带rmpA毒力基因的质粒.除了二元质粒外,还发现了两种可介导rmpA和KPC-2共同传播的融合质粒.研究人员通过捕获其祖先质粒,提出了该融合质粒的形成机制.此外,发现了五种rmpA启动子变异体(P9T到P13T),其活力与地理分布存在差异.通过CRISPR/Cas9基因编辑技术,证实活跃的“P11T-rmpA”调控子是“高风险”ST11-K64/CRKP克隆群的生物标志物.该研究拓展了对ST11-K64/Hv-CRKP流行性克隆的播散和临床演进的认知. The spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae(Hv-CRKP)is a global health concern.Here,we report the intrahospital colonization and spread of Hv-CRKP isolates in a tertiary hospital from 2017 to 2022.Analyses of 90 nonredundant CRKP isolates from 72 patients indicated that Hv-CRKP transferability relies on the dominant ST11-K64 clone.Whole-genome sequencing of 11 representative isolates gave 31 complete plasmid sequences,including 12 KPC-2 resistance carriers and 10 RmpA virulence vehicles.Apart from the binary vehicles,we detected two types of fusion plasmids,favoring the cotransfer of RmpA virulence and KPC-2 resistance.The detection of ancestry/relic plasmids enabled us to establish genetic mechanisms by which rare fusion plasmids form.Unexpectedly,we found a total of five rmpA promoter variants(P9T–P13T)exhibiting distinct activities and varying markedly in their geographic distributions.CRISPR/Cas9 manipulation confirmed that an active PT11-rmpA regulator is a biomarker for the"high-risk"ST11-K64/CRKP clone.These findings suggest clonal spread and clinical evolution of the prevalent ST11-K64/Hv-CRKP clones.Apart from improved public awareness of Hv-CRKP convergence,our findings might benefit the development of surveillance(and/or intervention)strategies for the dominant ST11-K64 lineage of the Hv-CRKP population in healthcare sectors.
作者 刘力彰 娄苧洁 梁琦强 肖伟 滕高钦 马剑钢 张会敏 黄曼 冯友军 Lizhang Liu;Ningjie Lou;Qiqiang Liang;Wei Xiao;Gaoqin Teng;Jiangang Ma;Huimin Zhang;Man Huang;Youjun Feng(Key Laboratory of Multiple Organ Failure,Ministry of Education,Department of Microbiology and General Intensive Care Unit of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;Zhejiang Academy of Agricultural Sciences,Hangzhou 310021,China;Cancer Center at Illinois,University of Illinois at Urbana-Champaign,Urbana,IL 61801,USA;Department of Clinical Laboratory,Shenzhen Third People’s Hospital,National Clinical Research Center for Infectious Diseases,The Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen 518112,China;Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering,Hangzhou 310058,China)
出处 《Science Bulletin》 SCIE EI CAS CSCD 2023年第23期3027-3047,M0006,共22页 科学通报(英文版)
基金 supported by the National Natural Science Foundation of China(32141001 and 31830001) the National Science Fund for Distinguished Young Scholars(32125003) the National Key R&D Program of China(2022YFC2303900 and 2022YFC3704700)。
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