Population structure in a fungal human pathogen is potentially linked to pathogenicity
Aspergillus flavus is a clinically and agriculturally important saprotrophic fungus responsible for severe human infections and extensive crop losses. Here, we analyze genomic data from 300 (117 clinical and 183 environmental) A. flavus isolates from 13 countries, including 82 clinical isolates sequenced in this study, to examine population and pan-genome structure and their relationship to pathogenicity. We use single nucleotide polymorphisms to build a phylogeny, analyze admixture, and perform discriminant analysis of principal components. We identify five A. flavus populations, including a new population, D, corresponding to distinct clades in the genome-wide phylogeny. Strikingly, > 75% of clinical isolates were in population D and <5% in population B. We also use orthogroup clustering to identify core and accessory genes within the pan-genome. Accessory genes, including genes within biosynthetic gene clusters, were significantly more common in some populations but rare in others. Our functional annotations show that population D is enriched for genes associated with carbohydrate metabolism, lipid metabolism and certain types of hydrolase activity, whereas a non-clinical population is depleted in genes related to zinc ion binding. In contrast to previous results from the major human pathogen Aspergillus fumigatus, isolation of A. flavus from human specimens is associated with population structure, providing a promising system for future investigations into the contributions of population-specific genetic differences to human infection.
Authors
- E. Anne Hatmaker (ORCID: https://orcid.org/0000-0002-7821-8160)
- Milton T. Drott (ORCID: https://orcid.org/0000-0001-9715-2200)
- Amelia E. Barber (ORCID: https://orcid.org/0000-0002-3399-1037)
- Thomas J. C. Sauters (ORCID: https://orcid.org/0000-0001-9524-2288)
- Justin L. Eagan (ORCID: https://orcid.org/0000-0002-1679-6117)
- Ana Alastruey‐Izquierdo (ORCID: https://orcid.org/0000-0001-8651-4405)
- Nancy P. Keller (ORCID: https://orcid.org/0000-0002-4386-9473)
- Dimitrios P. Kontoyiannis (ORCID: https://orcid.org/0000-0002-8051-2940)
- Oliver Kurzai (ORCID: https://orcid.org/0000-0002-7277-2646)
- Antonis Rokas (ORCID: https://orcid.org/0000-0002-7248-6551)
- Dea Garcia‐Hermoso (ORCID: https://orcid.org/0000-0001-5288-2904)
- Adiyantara Gumilang (ORCID: https://orcid.org/0000-0002-8887-9763)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- University of Wisconsin–Madison (US)
- Institut Pasteur (FR)
- Vanderbilt University (US)
- Université Paris Cité (FR)
- University of Würzburg (DE)
- Instituto de Salud Carlos III (ES)
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Cereal Disease Laboratory (US)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Vanderbilt Health (US)
- Medical Research Network (US)
- Friedrich Schiller University Jena (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-15
- DOI
- https://doi.org/10.1038/s41467-025-62777-9
- Citations
- 6
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 8.38
Funders
- National Science Foundation
- U.S. Department of Agriculture
- Burroughs Wellcome Fund
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Deutsche Forschungsgemeinschaft
- Robert Koch Institut
- National Institutes of Health
- Agricultural Research Service
- Instituto de Salud Carlos III
- National Eye Institute
- National Institute of Allergy and Infectious Diseases