# Evolutionary multispecies transcriptomics to reveal genes conferring pathogenicity within Leptospira spp

> **NIH NIH R21** · YALE UNIVERSITY · 2021 · $251,250

## Abstract

PROJECT SUMMARY
Leptospirosis is an emerging infectious disease and the leading zoonotic cause of morbidity and mortality
worldwide, with its greatest burden on subsistence farmers and urban slum populations. Leptospirosis causes life-
threatening disease and has emerged as a major cause worldwide of pulmonary hemorrhage syndrome (LPHS)
and acute kidney injury. To date, there is no effective prevention and control for leptospirosis in resource-poor
settings. In the US and other industrialized countries, leptospirosis is a major cause of disease among inner-city
populations, military personnel, and individuals engaged in swimming and water sports. Leptospirosis is caused by
environmentally transmitted spirochetes belonging to more than 300 serovars among seventeen pathogenic
species within the genus Leptospira, a genus that also comprises 26 non-pathogenic species and 21 intermediate
species, the latter with undefined role as disease causative agent. The hallmark of infection with Leptospira species
is its rapid hematogenous dissemination after the organism penetrates through mucous membranes, disseminating
to multiple organs throughout the host. Despite the sizable burden of disease associated with leptospirosis, the
biological and genetic mechanisms of pathogenesis associated with Leptospira remain poorly understood. This
crucial gap of knowledge has impaired the development of better diagnostic and control tools. In this exploratory
proposal, we hypothesize that shifts in gene expression, together with divergent and convergent evolution of gene
function, have led to diversity in ability of Leptospira to survive and thrive outside of the host and facultative
pathogenicity. To identify genes responsible for pathogenicity, we will use a comparative systems biological
approach, in which we profile transcription across species using in vitro models of infection that are in vivo
surrogates for gene expression. Those in vitro models mimic the epidemiological life cycle of the bacteria and the
biological processes essential to establish disease. Through access to our extensive library of himar1-based
mutants, we will identify strains with gene disruption for some of those targets. Through known functional
phenotypes using well-characterized in vitro assays of adherence and translocation, as well as ability to survive
and thrive in environmental matrices such as water and soil, we will determine and characterize the role of those
genes in pathogenicity and transmission. Acquiring knowledge of the identity of genes responsible for pathogenicity
and transmission is a major priority for the molecular understanding of the mechanisms of leptospiral pathogenesis
that will directly facilitate the advance of public health measures through the development of improved diagnostic
and prevention methods.

## Key facts

- **NIH application ID:** 10283483
- **Project number:** 1R21AI163663-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jeffrey Peter Townsend
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2021-07-09 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283483

## Citation

> US National Institutes of Health, RePORTER application 10283483, Evolutionary multispecies transcriptomics to reveal genes conferring pathogenicity within Leptospira spp (1R21AI163663-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10283483. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*