# Examining the role of opportunistic human pathogen Aspergillus flavus in fungal keratitis eye infections

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $30,878

## Abstract

Project Summary
 Aspergillus species are a leading cause of fungal infections in humans as the disease agents for both
aspergillosis respiratory infections and fungal keratitis (FK) eye infections. FK can necessitate a corneal
transplant or have the devastating consequence of blindness. Over a million new cases of FK are reported
annually worldwide. The primary risk factors for FK are contact lens use and surface scratches on the eye, which
allow infection of the cornea; damage occurs as the fungus grows into the cornea.
 The filamentous fungus Aspergillus flavus is a leading cause of FK infections and is isolated from FK
corneal ulcers more frequently than any other Aspergillus species, including closely related ones, such as A.
parasiticus, A. nomius, and A. arachidicola. A. flavus is known to grow at the temperature of the human body
(37°C), to produce bioactive secondary metabolites known as mycotoxins, and to tolerate high salinity levels, all
of which are thought to be relevant for infection and growth in the human eye. However, we do not understand
what genetic determinants of virulence are unique to A. flavus or how variation in these determinants contributes
to within- and between-species variation in the ability of A. flavus to cause FK.
 The goal of my project is to understand what makes A. flavus a successful pathogen when other closely
related, widespread Aspergillus species are not pathogenic as well as gain insights into variation in pathogenicity
within A. flavus. I hypothesize that the A. flavus genome includes unique genetic determinants of virulence absent
from related species. These may be genes or variants that are uniquely present or absent in A. flavus versus
closely related non-pathogens, such as genes involved in secondary metabolism (secondary metabolites often
affect host biology). We also do not yet know the genetic diversity, antifungal drug tolerance levels, or phenotypic
responses to heat or salinity of FK-causing A. flavus isolates. I hypothesize that genetic and phenotypic traits
differentially present in A. flavus and nonpathogenic relatives will also impact virulence.
 To test these hypotheses, I propose to first examine genomic diversity among Aspergillus species and
within A. flavus to identify putative genetic determinants of virulence, and to examine the impact of unique
determinants on virulence in an invertebrate model of disease. Second, I will investigate the impact of salinity,
heat, and antifungal drugs on growth phenotypes and chemical profiles of A. flavus and related species, and to
study the impact of secondary metabolites that are uniquely present in A. flavus on its virulence in an invertebrate
model of disease. The proposed experiments will enable me to identify key differences in genetic elements
between A. flavus and related species and provide a snapshot of population structure of clinical and
environmental isolates within A. flavus, as well as characterize the physiological responses of A. f...

## Key facts

- **NIH application ID:** 10388539
- **Project number:** 1F31EY033235-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Elizabeth Anne Hatmaker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $30,878
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388539

## Citation

> US National Institutes of Health, RePORTER application 10388539, Examining the role of opportunistic human pathogen Aspergillus flavus in fungal keratitis eye infections (1F31EY033235-01A1). Retrieved via AI Analytics 2026-08-03 from https://api.ai-analytics.org/grant/nih/10388539. Licensed CC0.

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