Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601  

作　　者：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 

机构地区：[1]Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [2]Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China [3]Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [4]Graduate School of the Chinese Academy of Sciences, Beijing 100039, China [5]Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China [6]National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing 102206, China

出　　处：《Cell Research》2011年第8期1210-1229,共20页细胞研究（英文版）

基　　金：We thank Professor M Picardeau for the gift ofL. interrogans strain IPAV and Bao-Yu Hu and Yang Yang for the support in performing bacteria culture. We also thank Dr Junwei Yang for suggestions in revising the manuscript. We thank the genome sequencing team at Chinese Human Genome Center at Shanghai for their assistance. This work was supported in part by grants from the National Natural Science Foundation of China （30770111, 30900051 and 30970125）, the National Key Program for Infectious Diseases of China （2008ZX10004 and 2009ZX10004）, the Program of Shanghai Subject Chief Scientist （09XD 1402700） and the Program of Shanghai Research and Development （10JC 1408200）.

摘　　要：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.

关 键 词：GENOME PROTEOME LEPTOSPIRA VIRULENCE MUTATION 

分 类 号：Q93[生物学—微生物学] S858.292[农业科学—临床兽医学]