1株致病性黄疸出血群钩端螺旋体病流行菌株与其同血清群疫苗株的比较基因组学分析  

Comparative genomic analysis of a pathogenic Leptospira Icterohaemorrhagiae circulating strain and vaccine strain of the same serogroup

作　　者：李彬 石刚 杜宗利 辛晓芳[1] 叶强[1] 徐颖华[1] LI Bin;SHI Gang;DU Zong-li;XIN Xiao-fang;YE Qiang;XU Ying-hua(NHC Key Laboratory of Biotechnology Product Verification Methods and Standardization,National Institutes for Foodand Drug Control,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院国家卫生健康委员会生物技术产品检定方法及其标准化重点实验室,北京1002629

出　　处：《中国生物制品学杂志》2022年第12期1432-1436,共5页Chinese Journal of Biologicals

基　　金：国家重点研发计划(2018YFC1603900);国家自然科学基金(81471968);医学微生物资源子平台运行与服务(NIMR-2021)。

摘　　要：目的对1株致病性黄疸出血群钩端螺旋体(简称钩体)病流行菌株与其同血清群疫苗株进行比较基因组学分析。方法应用高通量测序技术对黄疸出血群钩体流行株200502(简称流行株200502)进行全基因组序列测定,并与其同血清群疫苗株56601进行比较基因组学分析;选取GenBank中已公布的包括疫苗株56601在内的9株不同基因种的代表性钩体菌株构建系统发育进化树。结果流行株200502全基因组序列全长为4543190 bp,含有编码基因3580个,其中具有直系同源簇(clusters of orthologous groups,COG)功能2192个。流行株200502与疫苗株56601基因组平均核苷酸一致性为99.2%,存在共有基因3245个,流行株200502含有特有基因242个。以疫苗株56601为参考,在流行株200502中共鉴定出2005个插入缺失(indel)和19799个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,其中编码区有8485个同义SNP位点、3484个非同义SNP位点,涉及菌株的细胞运动、信号转导机制、防御机制等相关基因。流行株200502与L.interrogans、L.noguchii和L.kirschneri 3个基因种进化亲缘性较近。结论获得了我国当前黄疸出血群流行株200502基因组的基本特征,确定了其与血清型疫苗株56601的差异,为钩体疫苗的改进提供了实验依据。Objective To compare and analyze the complete genome of a pathogenic Leptospira Icterohaemorrhagiae(Leptospira for short)circulating strain and vaccine strain of the same serogroup.Methods The complete genome sequence of Leptospira Icterohaemorrhagiae circulating strain 200502(circulating strain 200502 for short)was determined by High-throughput sequencing technology,of which comparative genomic analysis was conducted with vaccine strain 56601 of the same serogroup.Genome-wide phylogenetic analysis of different Leptospira species were performed.Nine published representative Leptospira strains of various genetic species from GenBank,including vaccine strain 56601,were selected to construct phylogenetic evolutionary tree.Results The complete genome sequence of circulating strain 200502 was 4543190 bp in length and contained 3580 coding genes,of which 2192 had the function of clusters of orthologous groups(COG).The average nucleotide identity(ANI)between circulating strain 200502 and vaccine strain 56601 was 99.2%,with 3245 genes in common and 242 unique genes in circulating strain 200502.Taking vaccine strain 56601 as a reference,total 2005indels and 19799 single nucleotide polymorphism(SNP)sites were identified in the genome of strain 200502,of which 8485 synonymous and 3484 non-synonymous SNP sites in the coding region were involved in the related genes of cell movement,signal transduction mechanism,defense mechanism and so on.In addition,circulating strain 200502 was closely related to L.interrogans,L.noguchii and L.kirschneri species.Conclusion The basic genomic characteristics of the current Leptospira Icterohaemorrhagiae circulating strain 200502 were obtained,and the differences between the strain and serotype vaccine strain 56601 were determined,which provided a experimental basis for the improvement of Leptospira vaccine.

关 键 词：黄疸出血群钩端螺旋体 流行菌株 疫苗菌株 全基因组序列 比较基因组学 

分 类 号：R377.5[医药卫生—病原生物学]