Analysis Of Virulence Determinants And Immune Targets Based On Pathogenic Leptospire Omics Study

Leptospirosis is one of the most worldwide zoonoses caused by pathogenic Leptospira. Clinical presentations of the disease typically characterized as acute febrile il ness, jaundice and multisystem organ failure with hemorrhagic complication. It affects human health a lot and cause a loss to livestock meanwhile.But, research progresses of leptospira and leptospirosis have been slowly, for the lack of efficient genetic manipulation tools and unique phylogenetic status. The pathogenic mechanism is still unclear and suitable vaccines and diagnostic targets are also absence. However, since the first complete genome sequence of leptospire was published at 2003, genomics has provide a better understanding of the molecular evolution, metabolis m and pathogenicity of leptospira for us.Here, we sequenced the genomes of 11 standard strains of 15 Chinese prevalent serotypes. Based on the comparative analysis, the evolutionary relationship between these serotypes are clarified.And one of the strains 56610(401) was whole sequenced, a plasmid was confir med to be co-existed with two chromosomes in L.interrogans 56610(401) by PFGE and southern blot. One 56610(401) specific coding region of O-antigen biosynthesis loci(rfb) was recognized which might give convenience of serotype classification and identification of Leptospira. We further performed the comparative genomic study among two low virulent strains 56603(Gui44), 56610(401) and 6 reported whole genomes of leptospire. Finally, 20 core potential virulence genes were predicted.Moreover, during our study of surface-exposed proteome of L.interrogans str.56601, str.56603(Gui44) and str.56610(401), 81 core proteins and 61 dispensable proteins as well as 122 unique proteins were generated. Additionally, we identified one conserved secretory protein tpx(thiol peroxidase) which was encoded by LA0862. We demonstrated tpx of leptospire can be secreted to extracellular via atypical secretion pathway. And it will be up-regulated by hydrogen peroxide in vivo. These suggest tpx can protect leptospire through the process of interaction with the host. In addition, recombinant of leptospiral tpx could react with leptospirosis antiserum. Besides antiLA0862 serum has a cross response to 15 prevalent serotypes in China. It elucidated that LA0862 could be a favourable targets of vaccines and diagnosis and worthy of further more researches.