Genomic Analysis of Human-infecting Isolates in Sri Lanka: Expanded PF07598 Gene Family Repertoire, Less Overall Genome Reduction Than Bovine Isolates

commonly causes human leptospirosis, including severe disease. The first published analysis of , performed on two strains of serovar Hardjo (L550 and JB197), concluded that the genome is in the process of genome decay with functional consequences leading to a more obligately host-dependent life cycle. Yet whole genome analysis has only been carried out on few strains of , with limited closed genomes and comprehensive analysis. Herein we report the complete, circularized genomes of seven non-Hardjo isolates from human leptospirosis patients in Sri Lanka. These isolates (all ST144) were found to be nearly identical by whole genome analysis; serotyping showed they are a novel serovar. We show that the isolated from humans in Sri Lanka are less genomically decayed 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 published Hardjo genomes (L550, JB197 and TC112). Compared to previously published whole genome analyses showing two to three VM proteins in isolates from cattle, rats and humans, we found that all of the human isolates from Sri Lanka, including previously reported serovar Piyasena, have 4 encoded VM proteins, one ortholog of Copenhageni LIC12339 and 3 orthologs of LIC12844. 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 serovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of these isolates will enable deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis.