# Genetic Mechanisms of Sporulation Induction in C. difficile

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $460,874

## Abstract

Project Summary/Abstract
Clostridioides difficile (formerly Clostridium) is a major nosocomial pathogen that causes severe diarrheal
disease that is highly infectious and difficult to treat. C. difficile is easily transmitted due to the formation and
expulsion of contagious spores from infected hosts. The spore form of C. difficile is resistant to most disinfectants
and is critical for the survival of the bacterium outside of the host intestine. The gastrointestinal tract is the only
natural environment known to support C. difficile spore formation, but we understand little about how spore
formation is initiated by the bacterium. The long-term goal of this project is to uncover the molecular
mechanisms that control the initiation of C. difficile sporulation. Based on our data, we hypothesize that several
early sporulation proteins function in independent pathways to regulate the initiation of sporulation by controlling
activation of the master transcriptional regulator, Spo0A. The specific objectives of this application are to define
the direct regulatory mechanisms that act upon Spo0A and to delineate the molecular pathways that control
sporulation initiation. Capitalizing on our previous experiences in C. difficile molecular genetics, gene regulation,
and Gram-positive intestinal pathogenesis, we will meet the objectives through the experiments detailed in two
specific aims. In Aim 1, we will extend our current studies to uncover direct interacting partners of Spo0A using
a combination of genetic and biochemical approaches. In parallel, Aim 2 expands epistatic analyses to construct
Spo0A regulatory pathways, followed by functional analyses of the proteins within the initiation cascade. This
research is innovative because it combines biomolecular and genetic approaches to resolve a fundamental
question about this important and complex biological process. Completion of these aims is expected to expose
potential vulnerabilities in spore initiation. This work is an essential step in the development of rational strategies
to impede C. difficile transmission by preventing the formation of infectious spores in the host.

## Key facts

- **NIH application ID:** 10760271
- **Project number:** 5R01AI116933-09
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SHONNA M. MCBRIDE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,874
- **Award type:** 5
- **Project period:** 2015-08-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10760271

## Citation

> US National Institutes of Health, RePORTER application 10760271, Genetic Mechanisms of Sporulation Induction in C. difficile (5R01AI116933-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10760271. Licensed CC0.

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