Abstract:

Leptospirosis is a globally important zoonosis which affects people life and health. Our research group sequenced a representative virulent serovar type strain 56601 of Leptospira interrogans serogroup Icterohaemorrhagiae in 2003. The result revealed that Leptospira contains two chromosomes which encoded 4 727 genes. After that, we rectify and reannotate its genome to encode 3 718 genes. In 2010, the virulence-attenuated Leptospira interrogans serovar Lai strain IPAV was sequenced based on the reference sequence of strain 56601. Aside from their highly similar genomic structure and gene order, a total of 101 mutant genes were detected throughout the genome of IPAV. Using DNA microarray of Leptospira, the comparative genomic and genome-wide transcriptional analysis were conducted.  Among the 11 strains tested, the common backbone of the L.interrogans genome was estimated to contain about 2 917 protein-coding sequences (CDSs), while 275 CDSs were found absent from at least one strain. Moreover, two genomic islands (GIs) were firstly reported in strain 56601. Mimic the temperature that Leptospira encountered during infection of a host from an environmental source, expression of 106 genes differed significantly according to temperatures change. The differentially expressed genes belonged to nine functional categories. Through the differential gene expression between Leptospira interrogans serovar Lai type strain 56601 and its corresponding attenuated strain IPAV, a 22-kb genomic island covering a cluster of 34 genes (i.e., genes LA0186 to LA0219) was included, which was further confirmed to be a defect prophage. Combining computational prediction and high-accuracy tandem mass spectra, 2 540 proteins were detected. Subsequently, multiple posttranslational modifications (PTMs) of L.interrogans serovar Lai strain 56601 were detected, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features which were eukaryotic-like. Comparative proteomic analysis between 56601 and IPAV strain revealed 1 627 pairs of orthologs, 174 genes in the IPAV strain were upregulated and 228 genes in strain 56601 were upregulated.Based on the genomic and proteomic studies, some genes were selected to be further studied  to confirm their potential function on pathogenesis, vaccine and diagnosis.

Key words: Leptospira interrogans, genomics, proteomics