# High Throughput Screening for Non-antibiotic inhibitors of Clostridium difficile Pathophysiology

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $538,467

## Abstract

PROJECT SUMMARY/ABSTRACT
Clostridium difficile is the main cause of antibiotic-associated diarrhea. Since 2003, the incidence and severity
of C. difficile infection (CDI) has risen in the U.S. and globally. In the U.S. in 2011, there were ~29,000 deaths
from ~500,000 CDI cases. In 2013 the CDC designated C. difficile as an Urgent Threat. These trends were
related to the emergence of epidemic strains, in particular epidemic 027. Unfortunately, 20% or more of patients
treated with the antibiotics metronidazole or vancomycin, undergoes a recurrence, which is a further frustrating
feature of managing CDI, as the prognosis for patients with recurrent CDI is often poor. CDI recurrence partly
results from damage of the intestinal microbiota community by metronidazole or vancomycin. There is a need
for alternative treatments that are specific to disarming C. difficile without harming the gut microbiota. This is
addressed in the proposed study, which seeks to develop a novel high-throughput screening (HTS) platform for
discovering non-antibiotic compounds that specially inhibits C. difficile virulence, namely inhibiting cellular
production of toxins that are responsible for tissue damage and spores that are responsible for recurrence.
Preliminary data shows that such molecules do not harm the microbiota and reduce the onset of recurrent CDI
in animals. The study proposes to establish a HTS platform for toxin synthesis inhibitors, which is feasible owing
to state-of-the art facilities and resources at institutions involved in the study i.e. Texas A&M Health Science
Center, St Jude Children’s Research Hospital, Baylor College of Medicine and supporting research cores in the
Texas Medical Center. The team deploys a large compound collection for HTS, automated and semi-automated
screening technologies, and novel in vitro and in vivo microbiota models that are clinically reflective of CDI. The
studies outcome will be one or more candidate scaffolds that are suitable for lead optimization and drug
development. These molecules will help to probe ill-defined molecular pathogenic mechanisms to understand
the biology of this organism. Public health. The successful completion of this study impacts healthcare by
advancing candidate molecules for drug development to save lives by reducing the onset of CDI.

## Key facts

- **NIH application ID:** 10086387
- **Project number:** 5R01AI144459-03
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Julian G Hurdle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $538,467
- **Award type:** 5
- **Project period:** 2019-02-11 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086387

## Citation

> US National Institutes of Health, RePORTER application 10086387, High Throughput Screening for Non-antibiotic inhibitors of Clostridium difficile Pathophysiology (5R01AI144459-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10086387. Licensed CC0.

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