Nally, J. E. | Search bioRxiv

bioRxiv2024

Genomic Analysis of Human-infecting Leptospira borgpetersenii isolates in Sri Lanka expanded PF07598 gene family repertoire, less overall genome reduction than bovine isolates

Leptospira borgpetersenii commonly causes human leptospirosis, including severe disease. The first published analysis of L. borgpetersenii, performed on two strains of serovar Hardjo (L550 and JB197), concluded that the L. borgpetersenii 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 L. borgpetersenii, with limited closed genomes and comprehensive analysis. Herein we report the complete, circularized genomes of seven non-Hardjo Leptospira borgpetersenii 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 L. borgpetersenii 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 L. borgpetersenii Hardjo genomes (L550, JB197 and TC112). Compared to previously published L. borgpetersenii whole genome analyses showing two to 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 4 encoded VM proteins, one ortholog of L. interrogans 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 L. borgpetersenii serovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of these L. borgpetersenii isolates will enable deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis. Author SummaryLeptospirosis is an emerging bacterial zoonosis worldwide. Leptospira borgpetersenii predominates as the cause of human leptospirosis in some agricultural contexts. We address here the relatively neglected comparative genome analysis of L. borgpetersenii. We show here that L. borgpetersenii isolated from humans in Sri Lanka have less genome reduction compared to available cattle isolates and have novel virulence characteristics compared to isolates from other animals including cattle and rats.

microbiology↗

bioRxiv2024

Host population structure and rare dispersal events drive leptospirosis transmission patterns among Rattus norvegicus in Boston, Massachusetts, US

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus, is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity of Leptospira. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira isolates obtained from frozen and fresh tissue from some of the 59 Leptospira-positive rat kidneys. When isolates were not obtained, we attempted Leptospira genomic DNA capture and enrichment, which yielded 14 additional Leptospira genomes from rats. We also generated an enriched Leptospira genome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats, with specific clades tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.

molecular biology↗