By Caroline Cencer
Fungal diseases caused by pathogenic fungi such as molds affect millions of people worldwide every year. Despite the high prevalence of fungal diseases, the mechanism of infection is not well understood. The laboratory of Professor of Biological Sciences Antonis Rokas, led by graduate student Anne Hatmaker and in partnership with the lab of Nicholas Oberlies from the University of North Carolina Greensboro, set out to understand which traits influence the virulence, or severity of infection in humans, of a given fungal species.
One of the most common genera of infectious molds, Aspergillus fungi cause a range of respiratory infections upon inhalation. Hatmaker and colleagues discovered that not all species of Aspergillus are created equally, however. We sat down with Hatmaker to find out more about this study.
What issue/problem does your research address?
Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. In this study, we investigated Aspergillus flavus, a species of mold that can cause respiratory disease and/or inflammation of the eye; closely related species are not considered clinically relevant as they do not seem to infect patients as often. We looked at genomic and phenotypic (or observable) traits of four Aspergillus species—A. flavus, A. arachidicola, A. parasiticus, and A. nomiae—to see whether A. flavus differed from its relatives and determine which traits may impact its increased infection rates.
What was unique about your approach to the research?
The Rokas lab looks at disease causing properties, or pathogenicity, and virulence through the lens of evolution. We used Vanderbilt’s sequencing core, VANTAGE, to sequence the genomes of the four Aspergillus species used in this study. Conducting the DNA sequencing on campus was convenient and streamlined our study.
What were your findings?
We found that all four Aspergillus species, including the species not considered clinically relevant, can cause disease in animal models. Previous research has shown that growing Aspergillus molds at different temperatures can affect secondary metabolites, small organic molecules with potent bioactivities. In our study we found that temperature drastically impacted the number and type of secondary metabolites produced by the four fungal species. All four species produced more metabolites and shared more metabolites with other species at a higher temperature than at room temperature. Importantly, we saw major differences in the types of metabolites that different strains of the same species produced at room temperature, suggesting that not all members of a species can infect humans at the same rate. The extensive strain heterogeneity in virulence we observed does not correspond to the currently established clinical relevance of these species.
Where is this research taking you next? What will you personally be doing, or how will other researchers build on this work?
Dr. Rokas and I are very interested in the diversity within Aspergillus molds and the genetic differences we might find between strains of the same species, such as A. flavus. To study this, I’ve partnered with several collaborators around the world to sequence the genomes of 70 A. flavus samples isolated from human patients, making it the largest study of A. flavus clinical strains to date. I’ve combined these newly sequenced genomes with publicly available genomes from previous studies to amass a dataset with 250 strains of A. flavus. We’re currently comparing the genomes of the infectious patient strains with those that naturally occur in the environment—in the United States and abroad—to see whether there are any standout markers of virulence found in the patient strains. This identification could help us better understand the pathway of A. flavus infection in humans.
Funding was provided by the National Eye Institute, the National Science Foundation, the National Institute of Allergy and Infectious Diseases, and the Burroughs Wellcome Fund.
This paper, “Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives,” was published in Microbiology Spectrum in November 2022.