# Deciphering the phenotypic and genomic traits that underlie the evolution of pathogenicity differences among Aspergillus fumigatus and its close relatives

> **NIH NIH R56** · VANDERBILT UNIVERSITY · 2020 · $592,432

## Abstract

PROJECT SUMMARY
Aspergillus fumigatus is a major human fungal pathogen and an important threat to a variety of patient groups.
A few other closely related species in Aspergillus section Fumigati, are also pathogenic. In contrast, most other
closely related species in the section are either not known to be pathogenic or very rarely cause disease.
Pathogenic species appear to have originated repeatedly from non-pathogens, suggesting that pathogenicity
has evolved multiple times independently in this lineage. Furthermore, species on the pathogenic end of the
spectrum tend to be found in the environment in comparable numbers with species on the non-pathogenic end,
suggesting that the observed differences in pathogenicity are genetic.
 Several key traits are known to be associated with Aspergillus pathogenicity, such as the ability for fast
growth at high temperatures or in nutrient-limiting conditions and the ability to produce small, bioactive molecules
known as secondary metabolites. Similarly, several genes have been associated with Aspergillus fumigatus
virulence, although more await discovery. Surprisingly, little is known about how pathogenicity-related
traits and genes vary across pathogenic and non-pathogenic species belonging to the Aspergillus
section Fumigati. Hypothesizing that detailed functional and genomic comparisons between and within species
on the pathogenic end of the spectrum and species on the non-pathogenic end will identify new genetic factors
and key adaptations associated with the ability to cause human disease, this project aims to compare and
contrast Aspergillus species and strains spanning the pathogenicity spectrum at multiple levels of
biological and chemical complexity.
 We will achieve the goals of this project by carrying out three specific aims. In the first aim, we will
examine variation in the response to a range of key infection-relevant environments between and within species
spanning the pathogenicity spectrum. In the second aim, we will use the same set of strains to discover their
genomic and gene expression differences that control whether they are able to cause human disease or not. In
the third and final aim, we will describe the roles distinct genes play in fungal pathogenicity and analyze how
specific, or general, those contributions to fungal pathogenicity are to organisms across the section Fumigati.
 The proposed experiments will shed light on the biological, chemical, and genomic similarities and
differences between a set of very closely related species and strains spanning the pathogenicity spectrum, thus
advancing our understanding of the molecular foundations of the evolution of virulence in the genus Aspergillus,
one of the major genera associated with human fungal disease. More generally, our comparative and diverse
methods will aid in the establishment of a broader approach for understanding fungal disease and how major
pathogens can evolve from historically innocuous organisms.

## Key facts

- **NIH application ID:** 10241099
- **Project number:** 1R56AI146096-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Antonis Rokas
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $592,432
- **Award type:** 1
- **Project period:** 2020-09-04 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241099

## Citation

> US National Institutes of Health, RePORTER application 10241099, Deciphering the phenotypic and genomic traits that underlie the evolution of pathogenicity differences among Aspergillus fumigatus and its close relatives (1R56AI146096-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241099. Licensed CC0.

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