# Culture Independent Leptospira Comparative Whole Genome Analysis

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

## Abstract

PROJECT SUMMARY
This study is the culmination of years of careful preliminary work spent developing and validating a versatile
CWGA workflow that both improves upon the quality and reliability of available Leptospira genome data and is
capable of producing (and analyzing) these data directly from clinical samples — a crucial advance, as most
current studies avoid the cost of Leptospira culture. Crucial gaps in our understanding of Leptospira virulence and
pathogenetic mechanisms of disease persist due to the restricted scope, debatable quality and inherent bias of
publicly available genome data that blunt the power of CWGA. Our first objective here is to apply this new
approach to SMS data generated from a large biobank of 592 de-identified acute human serum samples (with
relevant demographic, clinical and epidemiological metadata) to identify Leptospira genes, with appropriate
sample distribution linked, linked to severe complications and poor outcomes (and) of human leptospirosis
presuming that these include reliable diagnostic targets and risk assessment markers (“prognostic indicators”).
Biobank sera originate from a recent NIH/NIIAID-funded prospective study of human leptospirosis in Sri Lanka
and include >400 from laboratory confirmed leptospirosis cases from which we obtained 25 Leptospira isolates
belonging to 5 discrete species and comprising at least 12 previously unreported serotypes. The low culture
success rate (<6%) — further confirmation of the desperate need for analytical tools that avoid Leptospira culture
— prompted development of a culture independent CWGA workflow featured in the current study. Next,
reliable candidate genes so identified will be used as substrates for qPCR assay development with subsequent
cross validation against a second large biobank of unrelated sera derived from a recent flood associated outbreak
of leptospirosis in Puerto Rico.
 Our success here should lay the groundwork for rapid development of antigen-detection diagnostic tests
and would have an immediate and profound impact on the Leptospira field. Moreover, untethered from the
inefficiency and bias of Leptospira culture, CWGA offers unprecedented insight into fundamental Leptospira
biology.

## Key facts

- **NIH application ID:** 10287936
- **Project number:** 1R21AI164106-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael A Matthias
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287936

## Citation

> US National Institutes of Health, RePORTER application 10287936, Culture Independent Leptospira Comparative Whole Genome Analysis (1R21AI164106-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10287936. Licensed CC0.

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