# C-di-AMP signaling in Clostridium difficile

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $192,446

## Abstract

Summary Abstract
Clostridium difficile causes diseases in humans ranging from antibiotic-associated diarrhea to potentially fatal
pseudomembranous colitis. It is well known that C. difficile disease symptoms are largely mediated by the
secreted cytotoxins produced during infection and that differentiation into metabolically dormant spores is critical
to transmission between hosts. However, much of the basic biology of this organism remains poorly understood,
including how C. difficile regulates adaptation to the host intestinal environment in response to extracellular
stimuli. Our long-term goal is to characterize the nucleotide second messenger signaling pathways controlling
virulence and transmission of C. difficile. The functions of the second messenger 3’,5’ cyclic diadenylic acid (c-
di-AMP) in C. difficile are completely unknown. In other bacterial species, c-di-AMP regulates growth, cell wall
homeostasis, antibiotic resistance, osmotolerance, potassium transport, metabolism, sporulation and/or immune
modulation. Preliminary data support a role for c-di-AMP in regulating C. difficile sporulation and other pathways
potentially affecting disease. Our central hypothesis is that c-di-AMP has broad effects on C. difficile physiology
through regulation of gene expression and protein function, with consequent effects on pathogenicity. We will
test our hypothesis by (1) using transcriptional and proteomic approaches to define the c-di-AMP regulon and
identify targets of c-di-AMP regulation, and (2) determining the impact of altering c-di-AMP on sporulation and
germination in vitro and virulence and transmission in vivo. These studies will determine the capacity of c-di-
AMP to influence the transmissibility and disease potential of C. difficile, and the findings will serve as the basis
of future work characterizing the c-di-AMP signaling pathway in C. difficile. Ultimately, these studies may identify
novel targets for inhibition of C. difficile virulence and transmission, which will help drive the much-needed
development of additional treatment and prevention options.

## Key facts

- **NIH application ID:** 9828522
- **Project number:** 5R21AI141373-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** RITA TAMAYO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,446
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828522

## Citation

> US National Institutes of Health, RePORTER application 9828522, C-di-AMP signaling in Clostridium difficile (5R21AI141373-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828522. Licensed CC0.

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