# Control of gut colonization by the prominent gut bacterium Bacteroides thetaiotaomicron

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $332,341

## Abstract

PROJECT SUMMARY
Bacteroides thetaiotaomicron is a beneficial gut bacterium strongly associated with lean and
healthy individuals. This proposal seeks to understand how colonization of the mammalian gut
by B. thetaiotaomicron is promoted by atypical forms of three highly conserved proteins: a
paralog of the essential translation factor EF-G, designated EF-G2; the essential transcription
termination factor Rho (BtRho), which harbors a ~300-residue long domain absent from
canonical Rho proteins and specifically required for gut colonization; and Roc, a transcriptional
regulator silenced by the simple sugars glucose and fructose. First, we will identify the
biochemical properties of EF-G2 that distinguish it from EF-G and render it necessary for gut
colonization, and test the hypothesis that EF-G2 is an energy-saving translation factor because it
lacks the guanosine triphosphate hydrolyzing activity in the presence of vacant ribosomes that
characterizes EF-G. Second, we will investigate the signals, genes, and regions of the extra
domain that determine liquid-liquid phase separation in BtRho and identify genes regulated by
the extra domain of BtRho. And third, we will determine how simple sugars control Roc amounts
via the 5' leader region of the roc mRNA and identify genes controlled by Roc when B.
thetaiotaomicron is in the murine gut. The proposed research will reveal novel biochemical
activities for widespread proteins and uncover novel colonization determinants. Moreover, it will
directly advance the engineering of commensal bacteria with desirable properties.

## Key facts

- **NIH application ID:** 10646419
- **Project number:** 5R01GM123798-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Eduardo Groisman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $332,341
- **Award type:** 5
- **Project period:** 2018-08-07 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10646419

## Citation

> US National Institutes of Health, RePORTER application 10646419, Control of gut colonization by the prominent gut bacterium Bacteroides thetaiotaomicron (5R01GM123798-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10646419. Licensed CC0.

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