# Polymicrobial interactions between co-infecting cystic fibrosis pathogens

> **NIH NIH FI2** · NATIONAL CANCER INSTITUTE · 2020 · —

## Abstract

ABSTRACT
In nature, microorganisms are typically found in multispecies communities, however most species are studied
in isolation. Polymicrobial interactions in infections affect pathogenesis by influencing nutrient availability,
colonization, and antibiotic resistance. In cystic fibrosis, a disease which is plagued by persistent respiratory
infections, the interactions of the bacterial pathogens Pseudomonas aeruginosa and Staphylococcus aureus
affect disease severity. It is common for bacteria to sense other microbes and respond antagonistically within
multispecies communities. Since P. aeruginosa frequently resides in multispecies environments and has the
capacity to secrete a plethora of antimicrobials, this proposal aims to investigate such a sensing and response
phenomenon between P. aeruginosa and S. aureus. It was recently discovered by our lab that P. aeruginosa
senses molecules released by S. aureus, and subsequently responds by producing antimicrobials that are
active against S. aureus, independent of the previously described bacterial cell wall sensing by P. aeruginosa.
The proposed research will take a multi-dimensional approach to analyze the polymicrobial interactions
between these co-infecting pathogens. To identify the specific S. aureus exoproducts that P. aeruginosa
senses, an array of promoter-reporters will be employed to determine active molecules by fractionating S.
aureus supernatant and using mass spectrometry, as well as by screening a S. aureus transposon library. The
antimicrobial response by P. aeruginosa will be characterized by global transcriptional analysis using RNA-seq.
Further, regulation of signaling cascades will be elucidated by Tn-seq, illuminating which genes are essential to
antimicrobial production. The known and novel antimicrobials induced by this interspecies sensing will be
determined by biochemical fractionation, identification of the active fractions with antimicrobial activity, and
mass spectrometry. Due to a surge in antibiotic resistance in both P. aeruginosa and S. aureus, and the effect
of these two pathogens on cystic fibrosis disease outcomes, it is imperative to elucidate the interactions
between these co-infecting pathogens. This work will yield new insight into interbacterial communication, and
reveal the molecular mechanisms governing antimicrobial production pathways that could be novel targets for
the development of therapeutics for chronic bacterial infections.

## Key facts

- **NIH application ID:** 10026395
- **Project number:** 1FI2GM137843-01
- **Recipient organization:** NATIONAL CANCER INSTITUTE
- **Principal Investigator:** Tiffany Zarrella
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026395

## Citation

> US National Institutes of Health, RePORTER application 10026395, Polymicrobial interactions between co-infecting cystic fibrosis pathogens (1FI2GM137843-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10026395. Licensed CC0.

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