# Mechanisms for sensing and responding to interbacterial antagonism

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $524,590

## Abstract

Project Summary
 It is increasingly evident that interspecies antagonism is intrinsic to life in the bacterial kingdom. And
yet, while our understanding of the antibacterial mechanisms bacteria employ in conflicts with their brethren
has recently grown exponentially, our knowledge of the means by which bacteria sense and respond to
antagonistic threats remains limited. In this proposal, we test the hypothesis that bacteria react to the presence
of an antagonistic bacterial competitor through the activation of a multifaceted defensive program. This
hypothesis grew from our discovery that Pseudomonas aeruginosa activates an extensive posttranscriptional
regulatory program in response to interbacterial antagonism. The pathway, which we term PARA
(Pseudomonas aeruginosa response to antagonism), is triggered when a subpopulation of P. aeruginosa cells
succumb to lysis as a result of an antagonistic attack. Detection of as yet unidentified molecule(s) in cellular
lysate leads to the activation of the small RNA-mediated Gac/Rsm global posttranscriptional regulatory
program. Activation of this response is crucial for P. aeruginosa survival during attack, as a mutant unable to
mount the response suffers a severe fitness defect during competition with antagonistic organisms. Finally, we
demonstrate that the defensive response requires multiple, simultaneously acting mechanisms, including
pathways of unknown function. In Aim 1 of this proposal, we will characterize one such pathway, which we
name ARC1 (antagonism response complex 1). Our preliminary data indicate that ARC1 is a large membrane-
associated protein complex that provides P. aeruginosa protection against antagonism mediated by toxins
delivered by the type VI secretion system of a competitor species. Our studies of ARC1 will elucidate the range
of threats towards which it provides protection and provide mechanistic insight into its defensive functions. In
Aim 2, we will pursue complementary genetic and biochemical approaches directed at characterizing the signal
present in P. aeruginosa cellular lysate responsible for triggering PARA. Finally, in Aim 3, we move beyond P.
aeruginosa and ask to what extent the regulatory components behind PARA – the Gac/Rsm pathway –
function generally to defend against interbacterial antagonism in other Pseudomonas species. We also
examine the hypothesis that variability in the Gac/Rsm regulon reflects adaptation to the specific bacterial
threats encountered by different species. Through this work, we stand to answer longstanding questions in the
field, including defining the evolutionarily relevant function of an important global regulatory program and
providing a molecular characterization of a long elusive signaling molecule. Additionally, through the
characterization of ARC1, our work will define the mechanistic basis for participation of a conserved membrane
complex of unknown function in interbacterial defense. Overall, the proposed work stands to broaden ou...

## Key facts

- **NIH application ID:** 10376201
- **Project number:** 5R01AI080609-13
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Joseph David Mougous
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $524,590
- **Award type:** 5
- **Project period:** 2009-06-17 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376201

## Citation

> US National Institutes of Health, RePORTER application 10376201, Mechanisms for sensing and responding to interbacterial antagonism (5R01AI080609-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376201. Licensed CC0.

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