# Bacterial Community Barrier to Vancomycin Resistant Enterococcus

> **NIH NIH R21** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2024 · $277,125

## Abstract

Current strategies to prevent resistance to specific antibiotics focus predominantly on reducing
inappropriate use of those antibiotics. However, colonization with vancomycin-resistant
Enterococci (VRE) in immunocompromised children is not predicted by prior vancomycin
treatment. This observation, also seen for other multidrug resistant organisms (MDRO),
suggests that other host and pathogen factors are pivotal drivers of the spread of antibiotic
resistance. Using VRE as a model MDRO, the objective of this study is to discover drivers on
both sides of the equation. On the host side—how human intestinal microbiome environment
selects VRE—and the pathogen side—which genes allow VRE to outcompete in microbial
communities. Using a combination of molecular, bioinformatic and population-level approaches,
the proposed experiments will test the central hypothesis that VRE colonization and domination
in humans requires disruption of both microbe-microbe and host-microbe interactions. This
proposal builds upon preliminary observations that human microbiome communities differ in
their ability block VRE colonization, and that VRE strains vary in their ability to overcome the
bacterial community barrier. The first aim will focus on identifying intestinal community microbes
that modulate VRE colonization. This will be evaluated using a priori bioinformatic predictions
and validated in community culture experiments. These experiments will pinpoint the
contributions of specific microbial community members by comparing VRE colonization in
diverse communities and sub-communities. Identification of microbiome interactions that
regulate MDRO colonization will enable exploration and discovery of new mechanisms to stop
spread of antibiotic resistance. The second aim will focus on identifying which bacterial genes
facilitate VRE colonization, persistence, and dominance. Genetic contribution to community
colonization will be tested in community cultures, utilizing both genetic knockouts of predicted
carriage genes and a broader survey with transposon-insertion libraries. This will yield
fundamental insight into how VRE persists in the absence of direct antibiotic selection. Overall,
this work will: i) identify microbiome disruptions that facilitate MDRO colonization for potential
amelioration, ii) inform infection prevention efforts by identifying strains likely to spread drug
resistance and uncover new microbiome interactions as novel anti-infective drug targets.

## Key facts

- **NIH application ID:** 10787020
- **Project number:** 1R21AI180489-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Elisa B H Margolis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $277,125
- **Award type:** 1
- **Project period:** 2024-06-04 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10787020

## Citation

> US National Institutes of Health, RePORTER application 10787020, Bacterial Community Barrier to Vancomycin Resistant Enterococcus (1R21AI180489-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10787020. Licensed CC0.

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