# Intestinal Enterococcal Dynamics: Modeling Host-Commensal and Host-Pathogen Interactions

> **NIH NIH R35** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $559,898

## Abstract

Abstract
The mammalian GI tract is colonized by trillions of microbes, which live in a predominantly symbiotic
relationship with their host and exert a profound affect on host physiology. Enterococcus faecalis is a common
colonizer of the mammalian gut and normally behaves as a symbiont. However, under certain circumstances,
E. faecalis acts as an opportunistic pathogen, invading from the gut and causing systemic infection. To gain a
better understanding of E. faecalis’s transition from symbiont to pathogen, we have developed a novel mouse
model of E. faecalis colonization that does not require disruption of the intestinal microbiota. This allows the
study of E. faecalis colonization during homeostasis. Our recent work, using this model, demonstrated the role
of enterococcal bacteriocins, plasmid-encoded antimicrobial peptides produced by E. faecalis, in intestinal
niche competition, and demonstrated a proof-of-concept that bacteriocin-producing E. faecalis can be used
therapeutically to eliminate colonization by multidrug resistant enterococcal strains. Cephalosporin treatment
of the mice induces E. faecalis expansion, invasion, and systemic spread, recapitulating the process seen in
human disease. Thereby, our model allows the study of several challenging questions regarding commensal
colonization and host interaction and the mechanisms that determine the balance between homeostasis and
disease. The focus of our work addresses the following key questions regarding host-commensal interaction:
1. What are the mechanisms that commensals, such as E. faecalis, use to adapt and colonize the intestines?
2. What are the host mechanisms that contribute to commensal colonization and containment? 3. How does
inflammatory or antibiotic disruption of the intestinal environment alter E. faecalis adaptation and drive
transition from symbiotic to pathogenic behavior? 4. What are the roles of bacteriocins in mediated bacterial-
bacterial and bacterial-host interaction? 5. Can we use our understanding of intestinal niche competition and
bacteriocin function to alter intestinal colonization to specifically eliminate multi-drug resistant bacterial
populations? A more complete understanding of the mechanistic contributions of both host and microbe to
commensal colonization will ultimately allow rational targeted manipulation of the microbiota for the prevention
and treatment of disease.
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## Key facts

- **NIH application ID:** 10234078
- **Project number:** 5R35GM122503-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Nita H Salzman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $559,898
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234078

## Citation

> US National Institutes of Health, RePORTER application 10234078, Intestinal Enterococcal Dynamics: Modeling Host-Commensal and Host-Pathogen Interactions (5R35GM122503-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10234078. Licensed CC0.

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