# Defining mechanisms of fungal-bacterial interactions during infection

> **NIH NIH K22** · CLEMSON UNIVERSITY · 2024 · $150,000

## Abstract

Project Summary
Aspergillus fumigatus (Af) is the most common and life-threatening airborne opportunistic fungal pathogen.
Investigations into Af pathogenesis have focused primarily on mono-species infections. The impact of co-
infecting microbes on Af physiology during infection remains an understudied but critically important research
area. Using cystic fibrosis (CF) infection as a model, my recent work has focused on characterizing Af physiology
in the presence and absence of the coinfecting bacterial pathogen, Pseudomonas aeruginosa (Pa), using multi-
omics approaches combined with reverse genetics. I have uncovered two major mechanisms of Af and Pa
interkingdom communication, mediated through the toxic, microbial secondary metabolites gliotoxin (produced
by Af) and hydrogen cyanide (produced by Pa). The proposed project builds logically on this work and aims to
uncover the mechanistic basis underlying the physiological shifts which occur in both organisms upon coculture
in synthetic CF sputum media. This work will also test if clinical isolates of Af and Pa maintain these secondary
metabolite response networks after chronic human infection and test to what extent polymicrobial interactions
impact Af physiology during human infection using advanced sequencing technologies. The overall goal of this
application is two-fold: 1) to define the specific molecular basis for interactions that occur between Af and Pa
(Specific Aim 1); and 2) to expand on these findings to determine the impact of microbial interactions and the
host environment on Af physiology during human CF infection (Specific Aim 2). This work is likely to yield
important discoveries that will aid in our understanding of both fungal physiology and the underlying mechanisms
of interkingdom microbial interactions within chronic polymicrobial infections.

## Key facts

- **NIH application ID:** 10580279
- **Project number:** 1K22AI174009-01
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Stephen K Dolan
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $150,000
- **Award type:** 1
- **Project period:** 2024-03-07 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580279

## Citation

> US National Institutes of Health, RePORTER application 10580279, Defining mechanisms of fungal-bacterial interactions during infection (1K22AI174009-01). Retrieved via AI Analytics 2026-07-19 from https://api.ai-analytics.org/grant/nih/10580279. Licensed CC0.

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