# Decoding interspecies signaling networks and the biogeography of polymicrobial infections

> **NIH NIH R35** · UNIVERSITY OF IOWA · 2022 · $386,250

## Abstract

PROJECT SUMMARY
Polymicrobial communities are ubiquitous in the human body and their behaviors are critical drivers of both
health and disease. Bacteria are social organisms; thus, the behavior of the group is driven not only by the
composition of the community, but also by interactions between the constituents and their surrounding
environment. A key principle shared among all communities, is that space matters. Groups organize to maximize
acquisition of goods, minimize exposure to toxic compounds, and optimize communication. Our recent data
reveal bacteria can communicate with members of distant species and respond by changing how they spatially
structure their communities. My laboratory seeks to understand how bacteria communicate between species by
observing them in their native environment, tracking their movements, and listening to and decoding their
languages.
We utilize Pseudomonas aeruginosa, the most notoriously problematic opportunistic pathogen in multiple types
of polymicrobial infections, including chronic wounds and lung infections in cystic fibrosis (CF) patients. We
recently reported that P. aeruginosa establishes infections with other important pathogens in the lungs of patients
with CF for decades, remaining unresponsive to intense antibiotic therapies and causing lung decline and early
death.
In this proposal, we begin by visualizing the spatial landscape of polymicrobial communities in situ, in
transplanted lungs from CF patients and animal models of polymicrobial infection. By combining next-generation
tissue clearing and fluorescent in situ hybridization, we are able to visualize the spatial positioning of species on
a range of spatial scales, in relation to each other and host structures. This will yield an unprecedented view of
microbes during infection and provide a platform for visualizing communities in other organs rich in polymicrobial
communities, such as the gastrointestinal tract.
Next, we will systematically decode the interspecies signaling language. We designed high-throughput screens
to identify genes necessary for signaling and the repertoire of signaling molecules. Using live-imaging techniques
pioneered by my lab, we visualize and track the movement of bacterial cells, gene expression, and dynamics of
motility appendages, upon modulation of the identified pathways. Initial studies reveal P. aeruginosa responds
by activating multiple signaling systems, which tune the direction of movement and activate virulence systems.
Collectively, these studies will construct a comprehensive picture of interspecies communication and enlighten
how interactions exacerbate disease.

## Key facts

- **NIH application ID:** 10471287
- **Project number:** 5R35GM142760-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Dominique Limoli
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2021-08-18 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471287

## Citation

> US National Institutes of Health, RePORTER application 10471287, Decoding interspecies signaling networks and the biogeography of polymicrobial infections (5R35GM142760-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10471287. Licensed CC0.

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