Genomic analysis of human-infecting Leptospira borgpetersenii isolates in Sri Lanka: Expanded PF07598 gene family repertoire and less genome reduction than bovine isolates

Leptospira borgpetersenii is a causative agent of human leptospirosis, with the potential to lead to severe disease manifestations. The first published analysis of L. borgpetersenii, performed on two strains of serovar Hardjo (L550 and JB197), suggested that the L. borgpetersenii genome is in the process of genome decay with functional consequences leading to a more obligately host-dependent life cycle. Whole genome analysis has only been carried out on few strains of L. borgpetersenii, with limited closed genomes and comprehensive analyses. Herein we report the complete, circularized genomes of seven non-typeable Leptospira borgpetersenii isolates from human leptospirosis patients in Sri Lanka. These isolates (all identified as strain ST144) were found to be nearly identical by whole genome analysis; serotyping with serogroup-specific reference antisera was unreactive, suggesting that these are members of a novel serogroup/serovar. We show that the L. borgpetersenii isolated from humans in Sri Lanka show less genomic decay than previously reported isolates: fewer pseudogenes (N = 141) and insertion sequence (IS) elements (N = 46) compared to N = 248, N = 270, and N = 400 pseudogenes, and N = 121 and N = 116 IS elements in other published L. borgpetersenii Hardjo genomes (strains L550, JB197 and TC112). Compared to previously published L. borgpetersenii whole genome analyses showing two or three VM proteins in L. borgpetersenii isolates from cattle, rats and humans, we found that all of the human L. borgpetersenii isolates from Sri Lanka, including previously reported serovar Piyasena, have four encoded VM proteins, one ortholog of L. interrogans Copenhageni LIC12339 (LA1402) and three orthologs of LIC12844 (LA0589). Our findings of fewer pseudogenes, IS elements, and expansion of the LIC12844 homologs of the PF07598 family in these human isolates suggests that this newly identified L. borgpetersenii serovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of these L. borgpetersenii isolates offer deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis.