# Polymicrobial interactions between commensal obligate anaerobic bacteria and cystic fibrosis pathogen P. aeruginosa

> **NIH NIH FI2** · NATIONAL CANCER INSTITUTE · 2021 · —

## Abstract

ABSTRACT
It has become apparent that the human microbiota impacts virtually every facet of human health, including
directly influencing clinical outcomes for certain diseases. The mechanisms that mediate these effects are
often the polymicrobial interactions between incoming pathogens and commensal microbes. In Cystic Fibrosis
(CF), a genetic disease in which patients are often afflicted with chronic bacterial infections, most notably
Pseudomonas aeruginosa, the effect of the resident anaerobes in disease outcome is conflicting and poorly
studied. However, microbiota-based studies have revealed that specific resident obligate anaerobic respiratory
bacteria are associated with improved CF outcomes, and limited evidence suggests that specific obligate
anaerobic bacteria impair P. aeruginosa colonization. Indeed, I recently discovered that the obligate anaerobic
respiratory bacterial species Porphyromonas catoniae inhibits P. aeruginosa growth by a contact-independent
mechanism. Genomic mining of the P. catoniae genome revealed no gene clusters known to be associated
with antimicrobial synthesis, we therefore hypothesize that P. catoniae inhibits P. aeruginosa by a novel
mechanism. The proposal will take a multifarious approach to investigate P. catoniae inhibition of P.
aeruginosa. To this end, a P. catoniae transposon mutant strain library will be constructed and screened to
identify the gene(s) responsible for inhibitory activity. Mass spectrometry will be utilized to characterize the P.
catoniae “secretome” to identify potential anti-P. aeruginosa compound(s). The P. aeruginosa global
transcriptional response to P. catoniae will be examined and measured by RNA-seq. Moreover, P. aeruginosa
Tn-seq will be used to illuminate which genes are associated with survival in the presence of P. catoniae.
Furthermore, we will assess the effects of bacterial lifestyle (planktonic vs. biofilm), CF relevant environmental
stimuli, and the addition of other obligate anaerobic respiratory bacteria on this interaction. Alternations in
biofilm biogeography under CF relevant conditions including the presence of other commensals will be
assessed with fluorescence confocal microscopy. En masse, this proposal seeks to provide novel insight into
interbacterial behavior and lifestyle that ultimately could reveal novel antimicrobials and/or molecular target(s)
to treat chronic P. aeruginosa infections and improve the clinical outcomes for CF patients.

## Key facts

- **NIH application ID:** 10275319
- **Project number:** 1FI2GM142805-01
- **Recipient organization:** NATIONAL CANCER INSTITUTE
- **Principal Investigator:** Britney Lashawn Hardy
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275319

## Citation

> US National Institutes of Health, RePORTER application 10275319, Polymicrobial interactions between commensal obligate anaerobic bacteria and cystic fibrosis pathogen P. aeruginosa (1FI2GM142805-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275319. Licensed CC0.

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