# Spore germination pathway in Clostridioides difficile and its pharmacological intervention

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2024 · $770,512

## Abstract

ABSTRACT
 Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the gut of patients treated with
broad-spectrum antibiotics. A challenge in treating C. difficile infection (CDI) is the production of spores that
germinate to active vegetative cells in response to host bile acids. The normal gut microflora typically prevents
colonization of C. difficile. Gut microflora dysbiosis as a consequence of treatment with broad-spectrum
antibiotics causes recurrence of CDI in 25% of patients, for which spore germination is an instigator. There are
no antibiotics for the treatment of multiple recurrent CDI, leading to 11,500 annual deaths in the United States.
CDI is the deadliest of the five bacterial urgent threats. Understanding the process of spore germination is key
to elucidating the basis for recurrent CDI. If spore germination could be prevented, the nefarious cycles of CDI
can be interrupted. We disclose the discovery of the oxadiazoles with bactericidal activity against C. difficile
vegetative cells, of which certain oxadiazoles also inhibit spore germination. This grant proposal is outlined in
three Specific Aims. We disclose our efforts in elucidation of the details of the spore-germination pathway
(Specific Aim 1). We have proposed experiments to demonstrate that inhibition of spore germination is at the
root of recurrence of CDI (Specific Aim 2). Furthermore, we outline our efforts to intervene pharmacologically in
recurrent CDI by inhibition of spore germination (Specific Aim 3).

## Key facts

- **NIH application ID:** 10853233
- **Project number:** 1R01AI178776-01A1
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Mayland F Chang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $770,512
- **Award type:** 1
- **Project period:** 2024-08-09 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853233

## Citation

> US National Institutes of Health, RePORTER application 10853233, Spore germination pathway in Clostridioides difficile and its pharmacological intervention (1R01AI178776-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10853233. Licensed CC0.

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