# Mechanisms Underlying Nutrient-Mediated Sporulation in C. difficile

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $465,918

## 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 up to 108 spores/ml of stool 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. Unfortunately, little is
known about the intestinal signals that lead to spore formation. The long-term goal of this investigation is to
uncover how nutrition drives C. difficile pathogenesis and transmission. The specific objectives of this
application are to determine which distinct nutritional pathways and effectors have the greatest impact on spore
production, and how these effects are regulated. Based on our data, we hypothesize that specific intestinal
metabolites promote toxin expression and spore formation, while other metabolites impede these processes.
The rationale underlying these studies is that uncovering the nutritional cues that drive the production of spores
will help us understand how disease and transmission occur. In our preliminary studies, we identified specific
nutrients that have dramatic effects on C. difficile spore formation. Capitalizing on our previous experiences in
C. difficile molecular genetics, metabolic gene regulation, and Gram-positive intestinal pathogenesis, we will
meet the objectives through the experiments detailed in two specific aims. To begin, we will define the specific
pathways affected by these compounds and then evaluate the impact of influential nutrients on C. difficile spore
formation and transmission. In parallel, we will dissect the regulatory mechanisms that link specific nutrients to
spore formation. This research is innovative because it takes advantage of the latest information about the
intestinal environment that supports CDI, and combines biochemical and genetic approaches to answer
fundamental questions about this important and complex biological process. The expected contribution of this
research is a detailed understanding of the relevant bacterial pathways that enable C. difficile sporulation in
response to specific nutrients. Moreover, 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:** 10413237
- **Project number:** 5R01AI156052-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SHONNA M. MCBRIDE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $465,918
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413237

## Citation

> US National Institutes of Health, RePORTER application 10413237, Mechanisms Underlying Nutrient-Mediated Sporulation in C. difficile (5R01AI156052-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10413237. Licensed CC0.

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