# Secreted antimicrobial proteins of the intestinal Bacteriodales

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $429,853

## Abstract

Project Summary
The intestinal microbiota is extremely important to human health and development. Over the last decade,
there has been a tremendous surge in the number of studies analyzing the gut microbiota; however, there are
still relatively few mechanistic studies aimed at understanding basic biological properties of this ecosystem and
its members. In recent years, our lab has been studying how predominant gut Bacteroidales members interact
with each other in both beneficial and competitive/antagonistic relationships. These studies are essential to
understanding how these bacteria become established in the mammalian intestine to form stable health-
promoting communities. This proposal is a continuation of our studies of antagonism among these bacteria,
specifically studying secreted antimicrobial molecules produced by the gut Bacteroidales. Under the initial
project, we made unexpected findings regarding the types of secreted antimicrobial molecules produced, the
range of Bacteroidales species that secrete antimicrobial molecules, and the mechanisms of resistance in
producing strains. The goal of this renewal project is to understand the breadth of secreted antimicrobial
molecules produced by the gut Bacteroidales, their targets and mechanisms of action in sensitive cells, and
their importance in mediating competition, invasion and defense in the mammalian gut microbiota. In Aim 1,
we will study a large class of proteins with membrane attack/perforin domains produced by diverse gut
Bacteroidales using predictive data to determine which of these molecules have antimicrobial activity and how
they target sensitive cells. In Aim 2, we will study a eukaryotic-like ubiquitin molecule with antimicrobial
activity, likely acquired by B. fragilis by inter-kingdom transfer, and determine its target and mechanism of
action. Aim 3 is designed to analyze the breadth of antimicrobial molecules produced by the gut Bacteroidales
by studying diverse Bacteroidales species that produce potent secreted antimicrobial molecules of different
classes. In Aim 4, we will use a combination of analyses, including computational modeling, experimental
analyses in gnotobiotic mice, and analyses of human metagenomic datasets to understand the ecological
relevance of secreted antimicrobial molecules of the gut Bacteroidales and how they contribute to ecosystem
invasion, defense, and stability. Currently, we are the only group studying secreted antimicrobial proteins of
the gut Bacteroidales and their ecological implications. The comprehensive analyses that will be performed in
this proposal are unprecedented in the field and the ecological properties that we uncover will serve as guiding
principles that can be applied to numerous human health applications such as restoring a healthy microbiota to
dysbiotic patients, and the creation of improved probiotics.

## Key facts

- **NIH application ID:** 9984265
- **Project number:** 5R01AI093771-09
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** LAURIE E COMSTOCK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,853
- **Award type:** 5
- **Project period:** 2012-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984265

## Citation

> US National Institutes of Health, RePORTER application 9984265, Secreted antimicrobial proteins of the intestinal Bacteriodales (5R01AI093771-09). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/9984265. Licensed CC0.

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