摘要
目的通过探究健康人群肠道中携带的blaNDM-1基因的肺炎克雷伯菌的基因组特征,明确健康人肠道定植菌及病原菌的耐药基因组,建立以耐药质粒基因组完成图为基础的耐药质粒监管体系。方法对健康人群肠道耐药菌监测中携带blaNDM-1基因的肺炎克雷伯菌开展抗菌药物敏感性实验,同时进行二代和三代测序以获得菌株及质粒全基因组完成图,利用核心基因组及泛基因组方法对该株菌进行序列比对分析,并进行接合转移实验确定质粒转移效率及最优转移条件。结果基于完成图的序列分析,发现本研究中所获得的肺炎克雷伯菌与来自公共数据库中的临床感染患者的菌株属于同一流行克隆,提示该克隆既可以引起人体感染,也可定植在健康人肠道内。明确blaNDM-1基因所在质粒为IncX3型,是易于携带blaNDM-1基因的流行质粒,泛基因组分析发现该类质粒可以突破宿主菌的种属屏障进行跨宿主传播;接合转移实验显示该质粒可转移、介导高水平的碳青霉烯类抗生素耐药性的传递。结论携带blaNDM-1基因的肺炎克雷伯菌可以在健康人肠道中定植,并通过耐药质粒实现耐药基因的跨宿主及宿主菌传播。因此有必要加强对健康人肠道定植菌群以及病原菌的耐药基因组监测、并建立以耐药质粒基因组完成图为基础的耐药质粒监管体系,能够从耐药基因转移因子的特征上进一步揭示耐药性传播的风险和人群扩散途径。
Carbapenems are considered the antibiotics of choice for the treatment of infections caused by multi-drug resistant gram-negative bacteria.The transmission of plasmid-mediated carbapenem resistance has become a public health issue.Numerous reports have described detection of carbapenem antibiotic resistance genes(ARGs)in patients and animals.However,the carbapenem ARGs carried by healthy individuals have been largely ignored,although healthy individuals may spread resistant bacteria.In this study,we report the isolation of carbapenem-resistant Klebsiella pneumoniae from a healthy person.The complete sequence was obtained through short-and long-read sequencing.Replicon type analysis,phylogenetic analysis and pan-genomic analysis were performed.The plasmid’s transfer ability was measured in various conjugation conditions.Two plasmids were identified.The bla NDM-1 gene was found in the IncX3 plasmid,which is often involved in bla NDM-1 gene transmission worldwide.The bla NDM-1-positive plasmid was transferable.Pan-genomic analysis indicated that bla NDM-1-carrying plasmids might be transmitted among distinct species and show cross-host spreading.K.pneumoniae isolated in this study belonged to an agenomic clonal cluster including several strains isolated from infected patients,thus suggesting that this clone can cause infection and colonize in testines in healthy humans.Our findings indicate a need for monitoring antibiotic-resistant bacteria,plasmids,and ARGs in healthy individuals,and for performing complete plasmid genome sequencing and comparison to monitor ARG spread and perform source tracing.
作者
曾薇
罗铭
刘佳琦
李哲
吴炎农
卢昕
阚飙
ZENG Wei;LUO Ming;LIU Jia-qi;LI Zhe;WU Yan-nong;LU Xin;KAN Biao(School of Public Health,Shandong University,Jinan 250012,China;National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;Yulin Center for Disease Control and Prevention,Yulin 537000,China;School of Food and Chemical Engineering,Beijing Technology and Business University,Beijing 100048,China)
出处
《中国人兽共患病学报》
CAS
CSCD
北大核心
2023年第3期221-227,共7页
Chinese Journal of Zoonoses
基金
国家重点研发项目(No.2020YFE0205700,No.2022YFC2303900)
国家自然科学基金(No.22193064)
国家科技重大专项(No.2018ZX10714002)
中国传染病预防控制国家重点实验室科学基金(No.2022SKLID303)联合资助。
