# Mechanism of Colonization Resistance

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $547,932

## Abstract

PROJECT SUMMARY
Antibiotic treatment impairs colonization resistance, thereby increasing the risk of infection with
Enterobacteriaceae that are frank (e.g. non-typhoidal Salmonella serovars) or opportunistic (e.g.
carbapenem-resistant Enterobacteriaceae) pathogens. However, how the host contributes to
colonization resistance against pathogenic Enterobacteriaceae remains incompletely understood.
The host uses “habitat filters” to select for microbial traits permitting survival and growth in the
host, thereby shaping composition, spatial organization and size of microbial communities. Our
goal is to elucidate how the host contributes to colonization resistance against pathogenic
Enterobacteriaceae and to develop approaches aimed at restoring this nonspecific immune
function during antibiotic therapy. We hypothesize that a mechanistic understanding of how the
host contributes to colonization resistance against pathogenic Enterobacteriaceae will facilitate
the development of drugs that target host signaling pathways to strengthen colonization
resistance. We will test different aspects of our hypothesis in two specific aims. Specific Aim 1
will identify resources that a shift in epithelial metabolism provides for pathogenic
Enterobacteriaceae to overcome niche modification by microbiota-derived short-chain fatty acids.
Specific Aim 2 will provide a proof-of-principle for the idea drugs targeting the host can strengthen
colonization resistance, thus making it possible to preserve this nonspecific immune function
during active antibiotic therapy. Successful completion of the proposed work will provide
mechanistic insights into a key function of the microbiome, which will be of wide appeal among
researchers interested in microbial pathogenesis, microbiota research, and intestinal biology.

## Key facts

- **NIH application ID:** 10793636
- **Project number:** 5R01AI112949-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Andreas J Baumler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $547,932
- **Award type:** 5
- **Project period:** 2014-08-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793636

## Citation

> US National Institutes of Health, RePORTER application 10793636, Mechanism of Colonization Resistance (5R01AI112949-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10793636. Licensed CC0.

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