Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601
Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601
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DOI：
10.1038/cr.2011.46
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发表时间：
2011-03
期刊：
影响因子：
44.1
通讯作者：
Y. Zhong;Xiao Chang;Xingjun Cao;Yan Zhang;Huajun Zheng;Yongzhang Zhu;Chengsong Cai;Zelin Cui;Yunyi Zhang;Yuan-yuan Li;X. Jiang;Guo-Ping Zhao;Shengyue Wang;Yixue Li;Rong Zeng;Xuan Li;Xiao-kui Guo
中科院分区：
文献类型：
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作者：
Y. Zhong;Xiao Chang;Xingjun Cao;Yan Zhang;Huajun Zheng;Yongzhang Zhu;Chengsong Cai;Zelin Cui;Yunyi Zhang;Yuan-yuan Li;X. Jiang;Guo-Ping Zhao;Shengyue Wang;Yixue Li;Rong Zeng;Xuan Li;Xiao-kui Guo
问号钩端螺旋体赖型IPAV毒力减毒株是从我国分离的一株高毒力祖先株经长期实验室传代而获得的。我们通过与致病性L.问号赖型56601株。测定了IPAV株的全基因组序列，并与56601株的全基因组序列进行了比较、校正和重新注释。除了基因组结构和基因序列高度相似外，在整个IPAV基因组中共检测到33个插入、53个缺失和301个单核苷酸变异（SNV），直接影响101个基因，无论是在其5′上游区域还是在其编码区。其中，44个功能基因中的大多数参与信号转导、胁迫响应、跨膜转运和氮代谢。基于定量液相色谱（LC）-MS/MS数据的比较蛋白质组学分析显示，在选择的1 627对直系同源物中，IPAV株中有174个基因上调，主要富集在能量产生和脂质代谢类中。相比之下，菌株56601中的228个基因被上调，其中大多数富集在蛋白质翻译和DNA复制/修复的类别中。基因组学和蛋白质组学方法的结合表明，改变表达或关键基因的突变，如编码Ser/Thr激酶，碳饥饿蛋白CstA，谷氨酰胺合成酶，GTP结合蛋白BipA，核糖核苷酸二磷酸还原酶和磷酸转运蛋白，以及脂蛋白或外膜蛋白的翻译谱的改变可能是IPAV株毒力衰减的原因。
The virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was derived by prolonged laboratory passage from a highly virulent ancestral strain isolated in China. We studied the genetic variations of IPAV that render it avirulent via comparative analysis against the pathogenic L. interrogans serovar Lai strain 56601. The complete genome sequence of the IPAV strain was determined and used to compare with, and then rectify and reannotate the genome sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 33 insertions, 53 deletions and 301 single-nucleotide variations (SNVs) were detected throughout the genome of IPAV directly affecting 101 genes, either in their 5′ upstream region or within their coding region. Among them, the majority of the 44 functional genes are involved in signal transduction, stress response, transmembrane transport and nitrogen metabolism. Comparative proteomic analysis based on quantitative liquid chromatography (LC)-MS/MS data revealed that among 1 627 selected pairs of orthologs, 174 genes in the IPAV strain were upregulated, with enrichment mainly in classes of energy production and lipid metabolism. In contrast, 228 genes in strain 56601 were upregulated, with the majority enriched in the categories of protein translation and DNA replication/repair. The combination of genomic and proteomic approaches illustrated that altered expression or mutations in critical genes, such as those encoding a Ser/Thr kinase, carbon-starvation protein CstA, glutamine synthetase, GTP-binding protein BipA, ribonucleotide-diphosphate reductase and phosphate transporter, and alterations in the translational profile of lipoproteins or outer membrane proteins are likely to account for the virulence attenuation in strain IPAV.