title: Comparative proteogenomic analysis of the Leptospira interrogans virulence-attenuated strain IPAV against the pathogenic strain 56601.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xiao
authors.initials: X
authors.lastname: Chang
authors.forename: Xing-Jun
authors.initials: XJ
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huajun
authors.initials: H
authors.lastname: Zheng
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chengsong
authors.initials: C
authors.lastname: Cai
authors.forename: Zelin
authors.initials: Z
authors.lastname: Cui
authors.forename: Yunyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Xiu-Gao
authors.initials: XG
authors.lastname: Jiang
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhao
authors.forename: Shengyue
authors.initials: S
authors.lastname: Wang
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Guo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002876:Chromosomes, Bacterial; D005798:Genes, Bacterial; D014644:Genetic Variation; D006168:Guinea Pigs; D007921:Leptospira interrogans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D023421:Models, Animal; D008969:Molecular Sequence Data; D009154:Mutation; D020543:Proteome / Q000032:analysis*; D016415:Sequence Alignment; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D020543:Proteome