Comparative analysis of whole genome sequences of Leptospira spp. from RefSeq database provide interspecific divergence and repertoire of virulence factors

Leptospirosis is an emerging zoonotic and neglected disease across the world causing huge loss of life and economy. The disease is caused by Leptospira of which 605 sequenced genomes representing 72 species are available in RefSeq database. A comparative genomics approach based on Average Amino acid Identity (AAI), Average Nucleotide Identity (ANI), and Insilco DNA-DNA hybridization provide insight that taxonomic and evolutionary position of few genomes needs to be changed and reclassified. Clustering on the basis of AAI of core and pan-genome contradict clustering pattern on basis of ANI into 4 clusters. Amino acid identity based hierarchical clustering clearly established 3 clusters of Leptospira correlating with level of virulence. Whole genome tree supported three cluster classifications and grouped Leptospira into three clades termed as pathogenic, intermediate and saprophytic. Leptospira genus consist of diverse species and exist in heterogeneous environment, it contains relatively large and closed core genome of 1038 genes. Analysis provided pan genome remains open with 20822 genes. COG analysis revealed that mobilome related genes were found mainly in pan-genome of pathogenic clade. Clade specific genes mined in the study can be used as marker for determining clade and associating level of virulence of any new Leptospira species. Many known Leptospira virulent genes were absent in set of 78 virulent factors mined using Virulence Factor database. A deep search approach provided a repertoire of 496 virulent genes in pan-genome. Further validation of virulent genes will help in accurately targeting pathogenic Leptospira and controlling leptospirosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/426470v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@104babborg.highwire.dtl.DTLVardef@17f727dorg.highwire.dtl.DTLVardef@35a6c1org.highwire.dtl.DTLVardef@56fd53_HPS_FORMAT_FIGEXP M_FIG C_FIG