# Investigating the impact of collagenase in Clostridioides difficile pathogenesis

> **NIH NIH F31** · EMORY UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Clostridioides difficile is the leading cause of antibiotic-associated diarrhea, with over 223,000 infections, almost
13,000 deaths, and 1 billion dollars in healthcare cost in the United States every year. C. difficile infection starts
when infectious spores are ingested and germinate in the gastrointestinal (GI) tract to produce the vegetative
cells that cause the disease. In order to establish an infection, C. difficile must colonize the human colon,
however, the factors that allow C. difficile to successfully colonize the intestine remain largely unknown.
Hydrolytic enzymes such as collagenases and gelatinases have been known to help multiple pathogens to
colonize distinct niches within the human body by facilitating penetration into host tissues, contributing to the
dissemination of toxins, and increasing the availability of nutrients for the pathogen to use. These enzymes allow
the degradation of collagen and its derivative gelatin, which are ubiquitous components of mammalian tissues
(including gastrointestinal tissue). I hypothesize that the collagenase enzymes in C. difficile are colonization
factors that allow this bacterium to degrade host collagen and gelatin, and that these hydrolytic
activities improve C. difficile intestinal colonization and persistence in the gut to increase virulence. The
overall objective of this application is to identify what enzyme(s) are responsible for the collagenolytic and
gelatinolytic activities observed in C. difficile strains, and how these activities impact pathogenesis and the host.
To test this hypothesis, and in pursuit of the overall goal, I am determined to complete the following Specific
Aims: Aim 1. Determine the role of U32 peptidases CD0703 and CD1228 in collagen and gelatin degradation.
Aim 2. Examine the role of the collagenase/gelatinase in C. difficile pathogenesis and colonization of
the host intestine. The completion of these aims will identify the enzyme(s) responsible for the hydrolytic activities
observed in C. difficile and determine the contribution of these hydrolytic activities during C. difficile infection.
Elucidating these could provide novel targets for prevention or treatment of C. difficile infection.

## Key facts

- **NIH application ID:** 10588187
- **Project number:** 5F31DK126467-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** German Gabriel Vargas-Cuebas
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2020-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10588187

## Citation

> US National Institutes of Health, RePORTER application 10588187, Investigating the impact of collagenase in Clostridioides difficile pathogenesis (5F31DK126467-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10588187. Licensed CC0.

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