# Evolution of Aspergillus fumigatus virulence

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2020 · $454,942

## Abstract

A significant challenge faced by obligate aerobic eukaryotic pathogens during infection is
low oxygen microenvironments. The ability to acquire sufficient oxygen in the face of oxygen depletion has now
been shown to be critical for Aspergillus fumigatus and other eukaryotic pathogen's virulence. However, a
major gap in knowledge is how obligate aerobic fungi acquire oxygen in the face of oxygen depletion. An in
vitro experimental evolution experiment conducted under low oxygen conditions to identify mechanisms of A.
fumigatus hypoxia fitness revealed an unexpected change in the fungal mycelium, or biofilm, morphology. A
substantial increase in fungal colony furrowing, a so called rugose colony morphology, was observed in the
evolved strain with a concomitant increase in hypoxia fitness compared to the parental strain. Importantly, this
morphological change and increased hypoxia fitness strongly correlates with virulence. Examination of a large
collection of A. fumigatus strains with increased virulence and hypoxia fitness reveals similar colony
morphological changes. Preliminary whole genome sequencing of the evolved strain identified a mutation in a
novel unstudied fungal specific gene we currently call eefA. Over-expression or loss of eefA dramatically
affects fungal colony morphology, hypoxia fitness, and virulence. In this proposal, we will test the hypothesis
that increased colony furrowing represents a novel mechanism for fungal oxygen acquisition that is critical for
virulence. Using molecular genetics, biochemical, and host-pathogen interaction approaches, we will define the
novel function of eefA in mediating fungal oxygen acquisition and virulence. Preliminary data strongly link eefA
with the ability of hyphae to adhere and form furrows that promote oxygen access to fungal cells deep within
the mycelium. How fungal colony morphology and structure affects A. fumigatus virulence is unstudied and
represents a new paradigm for a mechanism of in vivo fitness in the face of low oxygen stress. Consequently,
the proposed studies will reveal new insights into A. fumigatus virulence mechanisms and are expected to
identify novel therapeutic approaches to thwart fungal oxygen acquisition in vivo to improve disease outcomes.

## Key facts

- **NIH application ID:** 9994815
- **Project number:** 5R01AI130128-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Robert Andrew Cramer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,942
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994815

## Citation

> US National Institutes of Health, RePORTER application 9994815, Evolution of Aspergillus fumigatus virulence (5R01AI130128-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994815. Licensed CC0.

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