首页|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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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, ribonucleotidediphosphate 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.

genomeproteomeLeptospiravirulencemutation

Yi Zhong、Xiao Chang、Xing-Jun Cao、Yan Zhang、Huajun Zheng、Yongzhang Zhu、Chengsong Cai、Zelin Cui、Yunyi Zhang、Yuan-Yuan Li、Xiu-Gao Jiang、Guo-Ping Zhao、Shengyue Wang、Yixue Li、Rong Zeng、Xuan Li、Xiao-Kui Guo

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Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China

Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Graduate School of the Chinese Academy of Sciences, Beijing 100039, China

Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China

National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing 102206, China

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This work was supported in part by grants from the National Natural Science Foundation of ChinaThis work was supported in part by grants from the National Natural Science Foundation of ChinaThis work was supported in part by grants from the National Natural Science Foundation of ChinaNational Key Program for Infectious Diseases of ChinaNational Key Program for Infectious Diseases of ChinaProgram of Shanghai Subject Chief ScientistProgram of Shanghai Research and Development

3077011130900051309701252008ZX100042009ZX1000409XD140270010JC1408200

2011

10.1038/cr.2011.46

细胞研究(英文版)
中国科学院上海生化细胞所

细胞研究(英文版)

CSTPCDCSCDSCI
影响因子：1.355
ISSN：
年,卷(期)：2011.21(8)
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