# Mechanism Of Enterococcus Faecalis Nitro Drug Metabolism And In Vivo Implications

> **NIH NIH R21** · UNIVERSITY OF TEXAS DALLAS · 2022 · $222,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Understanding drug metabolism by intestinal microbiota is at the forefront of research to explain why some
patients do not adequately respond to therapy. However, there remains a lack of research on infectious diseases
and the cellular mechanisms by which specific microbes metabolize antibiotic therapies and its impact on
treatment outcomes in patients. To advance this research area, we intend to elucidate how Enterococcus sp.
gut bacteria metabolize the nitro-containing drug metronidazole. Enterococcus faecalis and Enterococcus
faecium are the main colonizers of the human gut, and also cause opportunistic infections. Metronidazole is an
important therapy for Clostridioides difficile infection (CDI), a disease that poses an urgent threat to public health.
Furthermore, in CDI patients, colonization of with vancomycin-resistant enterococci (VRE) exacerbates disease
severity. E. faecalis, but not E. faecium, degrades metronidazole. Our preliminary data suggests this is due to
unique interactions between electrochemical components found in E. faecalis and absent in E. faecium. We will
now investigate how this mechanism operates in E. faecalis and the extent to which this bacterium promotes
treatment failure for metronidazole. In aim 1 we propose to use microbial genetics and metabolomics to elucidate
the mechanism(s) of metronidazole degradation and identify the metabolites formed. Aim 2 will co-culture
enterococcal and C. difficile species to identify and measure which species protect C. difficile from being killed
by metronidazole. Studies will progress to animals, where we measure the effect of enterococci on metronidazole
treatment outcomes and severity of CDI disease. This work will advance knowledge of enterococcal physiology
relating to its metabolism and aspects that differentiate E. faecalis from E. faecium. These exploratory studies
lay the foundation to understand inter-species interactions between enterococci and C. difficile and how this
influences disease development and progression. Public health. E. faecalis, E. faecium and C. difficile are
leading pathogens causing diseases in hospitals. This study has significant implications for the diagnosis and
treatment of CDI, a disease that imposes a major public health and economic burden in the United States.

## Key facts

- **NIH application ID:** 10511022
- **Project number:** 1R21AI171660-01
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Julian G Hurdle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $222,000
- **Award type:** 1
- **Project period:** 2022-06-03 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511022

## Citation

> US National Institutes of Health, RePORTER application 10511022, Mechanism Of Enterococcus Faecalis Nitro Drug Metabolism And In Vivo Implications (1R21AI171660-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10511022. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*