A core and pan gene map of Leptospira genus and its interactions with human host

Abstract

Leptospira species are the etiological agent of an emerging zoonotic disease known as “Leptospirosis” that substantially affects both human health and economy across the globe. Despite the global importance of the disease, pathogenetic features, host-adaptation and proper diagnosis of this bacteria remains lacking. To accomplish these gaps, pan-genome of Leptospira genus was explored in the present study. The pan-genome of Leptospira genus was comprised of core (692) and accessory parts (softcore:1804, shell:6432, cloud:16,600). The functional analysis revealed the abundancy of “Translation, ribosomal structure and biogenesis” COG class in core-genes; whereas in accessory parts, genes involved in signal transduction was the most abundant. Furthermore, pathogen-host interaction (PHI) analysis of core and accessory proteins with human proteins showed the presence of a total of 599 and 510 interactions, respectively. There were eight hubs in core PHI network and five hubs in PHI network of accessory proteins. The human's proteins involved in these interactions were found functionally enriched in metabolic processes, responses to stimulus and immune system processes. Further, pan-genome based phylogeny separated the Leptospira genus in three major clades (belonging to P1, P2 and S) which relates with their pathogenicity level. Additionally, pathogenic and saprophytic clade specific genes of Leptospira have also been identified and functionally annotated for COG, KEGG and virulence factors. The results revealed the presence of 102 pathogenic and 215 saprophytic group specific gene clusters. The COG functional annotation of pathogen specific genes showed that defence mechanism followed by signal transduction mechanisms category were most significantly enriched COG categories; whereas in saprophytic group, signal transduction mechanisms was the most abundant COG, suggesting their role in adaptation and hence important for microbe's evolution and survival. In conclusion, this study provides a new insight of genomic features of Leptospira genus which may further be implemented for development of better control actions of the disease.