# Polymicrobial interactions in the respiratory tract

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $391,250

## Abstract

ABSTRACT
Persistent polymicrobial respiratory infections in individuals with Cystic Fibrosis (CF) are a significant cause of
morbidity and mortality. The airway epithelium provides the first line of defense against respiratory infections and
is a critical component of the innate immune system, but the dysregulated immune response in the CF lung is
ineffective at clearing pathogens. Bacterial pathogens can displace commensal CF lung microbes to establish
chronic infections, and this decreased microbial diversity correlates with declining patient health. Progression of
CF respiratory disease is also influenced by coinfection with respiratory viruses. Acquisition of Pseudomonas
aeruginosa in CF patients correlates with seasonal respiratory virus infections, and CF patients experience
increased severe exacerbations and declines in lung function during respiratory viral coinfection. In light of our
recent report that P. aeruginosa biofilm growth in association with CF airway epithelial cells (AECs) is enhanced
during coinfection with respiratory viruses, and mediated by innate antiviral signaling, we hypothesize that virus
coinfection alters microbial community dynamics in the CF airways, disturbing the balance between bacterial
populations. To investigate this hypothesis, we will evaluate the impact of virus infection and the innate antiviral
response on mixed-species bacterial biofilms in a CF airway epithelial cell co-culture model and in vivo murine
model. Preliminary data show virus co-infection allows P. aeruginosa to outcompete Staphylococcus aureus in
polybacterial biofilms on CF AECs, and P. aeruginosa exhibits enhanced production of a key antimicrobial,
pyocyanin, during virus co-infection. The host innate antiviral immune response, through induction of
indoleamine 2,3-dioxygenase-1 (IDO1) activity and the tryptophan metabolite kynurenine, appear to regulate
pyocyanin induction. These results suggest previously unexplored roles for the host innate immune response
and immunometabolism in shaping microbial communities in the respiratory tract during virus co-infection. To
this end, we will (1) evaluate virus-specific and innate antiviral mechanisms influencing bacterial populations
during virus co-infection, (2) determine the antimicrobial mechanism(s) P. aeruginosa employs to outcompete S.
aureus during viral co-infection, and (3) evaluate the role of the host kynurenine pathway in mediating bacterial
competition during virus co-infection. These studies will provide a novel link between the host innate immune
response and metabolic processes in the epithelium that impact the propensity of bacterial pathogens to
persistently colonize the airways in CF. Our goal is to elucidate molecular mechanisms that govern viral-bacterial
interactions and shape host-associated microbial communities in CF and thus, identify new targets that could
delay acquisition and chronic bacterial colonization, or work in conjunction with existing therapies to eradicate...

## Key facts

- **NIH application ID:** 10125191
- **Project number:** 5R01HL142587-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jennifer Melinda Bomberger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125191

## Citation

> US National Institutes of Health, RePORTER application 10125191, Polymicrobial interactions in the respiratory tract (5R01HL142587-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10125191. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*