# Mechanisms of adaptation to interbacterial antagonism by the human gut microbiota

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2021 · $327,305

## Abstract

The impact of the gut microbiota on human health depends on the identity of the species
therein. The mechanisms that lead to differences in microbiota composition between people is
not well understood. We focus on interbacterial interactions between members of the dominant
taxon in the gut of Western adults, the order Bacteroidales. These bacteria compete for space
and nutrients via a molecular nanoweapon known as the type VI secretion system (T6SS). Toxic
protein effectors delivered between adjacent Bacteroidales cells by the T6SS result in cell statis
or lysis, and we and others have previously revealed that this competition results in strain-level
differences in the microbiota through exclusion of target bacteria via killing. Since effectors can
be delivered indiscriminately to kin cells, T6SS-encoding bacteria produce immunity factors that
specifically neutralize cognate effectors. We have previously identified the pervasive presence
of “orphan” immunity factors encoded within large genomic arrays within Bacteroidales
genomes that lack cognate effectors. These acquired interbacterial defense (AID) systems
render the T6SS ineffective through neutralization of cognate effectors and facilitate strain-
exclusion from microbiomes. In this proposal, we seek to understand the mechanism by which
orphan immunity genes are captured aggregated into the most common type of AID system, the
recombinase-associated AID (rAID) system, using a powerful combination of bacterial genetics,
biochemistry, metagenomics, and gnotobiology. We further seek to understand the regulation
and biogeographical role of rAID systems through a hypothesized “competition-sensing”
mechanism that involves a hybrid sensor-kinase pathway. Together, we aim to understand the
impact of Bacteroidales defense against the T6SS on the gut microbiome.

## Key facts

- **NIH application ID:** 10274748
- **Project number:** 1R35GM142685-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Benjamin Davidson Ross
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,305
- **Award type:** 1
- **Project period:** 2021-08-02 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274748

## Citation

> US National Institutes of Health, RePORTER application 10274748, Mechanisms of adaptation to interbacterial antagonism by the human gut microbiota (1R35GM142685-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274748. Licensed CC0.

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