# Mechanisms of Nutrient Competition in the Intestine

> **NIH NIH R01** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2020 · $292,555

## Abstract

PROJECT SUMMARY/ABSTRACT
The World Health Organization classifies diarrhea as a significant worldwide health threat, killing thousands of
children daily. Ingestion of a small number of infectious organisms can lead to trillions of pathogens being shed
in the stool. Therefore, we postulate that enteric pathogens such as enterohemorrhagic E. coli possess potent
mechanisms for obtaining nutrients that provide the energy needed to replicate rapidly in the intestine. While
many of the nutrients that support intestinal colonization by model organisms are known, the mechanisms
underlying competition for those nutrients are poorly understood. With NIH funding and a research strategy
built on the streptomycin treated mouse model, we previously identified the nutrients that support colonization
by six genome-sequenced, genetically tractable, prototypical pathogenic and commensal E. coli strains. While
these bacteria essentially use the same growth substrates in laboratory culture, each uses a different subset of
the available nutrients in the intestine. Indeed, different E. coli strains can co-colonize with one another,
indicating that they occupy distinct niches. Two commensal E. coli strains were found to exert colonization
resistance against E. coli O157:H7. On the other hand, two other pathotypes were able to overcome
colonization resistance to co-colonize with the same commensals. According to basic ecological principles, the
niches occupied by competing bacteria are defined by nutrient availability. An important prediction of the
nutrient-niche hypothesis is that resistance or sensitivity to invasion depends on nutrient consumption by the
resident microbiota, but there is little supporting evidence. Importantly, we recently proved that colonization
resistance is imparted by the facultative anaerobes. The question is: how do pathogens overcome colonization
resistance to initiate infections? In the streptomycin treated mouse model of competitive colonization, the
facultative microbiota can be manipulated to consist of carefully chosen, well-characterized commensal E. coli
strain(s) that either exert colonization resistance, or not, against selected pathotypes. The proposed research
strategy tests the hypothesis that successful invasion by enteric pathogens depends on potent mechanisms to
compete for the nutrients needed to replicate in the intestine. In Aim 1 the competitive colonization model will
be used to measure the nutrients that are available to invading pathogens and genome-specific RNA
sequencing will determine the catabolic gene systems that are induced in the competing E. coli pathogens and
commensals in the intestine. Aim 2 will focus on the mechanisms of nutrient competition between E. coli
pathogens and commensals by direct measurement of nutrient consumpition in vivo. To identify allelic
differences in catabolic genes that confer fitness advantages, catabolic operons will be swapped between
strains and their competitive fitness will be a...

## Key facts

- **NIH application ID:** 9853632
- **Project number:** 5R01GM117324-04
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** TYRRELL CONWAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $292,555
- **Award type:** 5
- **Project period:** 2017-03-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853632

## Citation

> US National Institutes of Health, RePORTER application 9853632, Mechanisms of Nutrient Competition in the Intestine (5R01GM117324-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853632. Licensed CC0.

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