Author:
EA Hatmaker1*, M Rangel Grimaldo2, RW Bastos3, H Pourhadi2, S Knowles2, K Fuller4, G Goldman3, N Oberlies2, A Rokas1
Author address:
1Biological Sciences, Vanderbilt University, Nashville, USA
2Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, USA
3Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
4Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, USA
Full conference title:
10th Advances Against Aspergillosis and Mucormycosis
Date: 2 February 2022
Abstract:
Purpose:
Although fungal diseases affect millions of humans each year, fungal pathogens of humans remain understudied. The mold Aspergillus flavus is a causative agent of both aspergillosis and fungal keratitis infections. Although A. flavus is commonly isolated from patients with these infections, species closely related to A. flavus are rarely, if ever, isolated from patients and are not considered clinically relevant. To gain insights into why this is the case, we compared genomic and phenotypic traits between A. flavus and three closely related non-pathogenic species, namely A. arachidicola and A. parasiticus, and A. nomius.
Methods:
We sequenced genomic DNA from seven strains, two each of A. arachidicola, A. parasiticus, and A. flavus, and one A. nomius. We assembled and annotated draft genomes and predicted biosynthetic gene clusters for each strain, and identified and compared orthologous proteins. Additionally, we characterized the secondary metabolite production of all seven strains in two clinically relevant conditions: the temperature of the human body and the salt concentration of human tears. We also examined the relative virulence of each strain using the invertebrate model of fungal disease Galleria mellonella.
Results:
Our genomic analyses revealed that A. flavus strains shared seven biosynthetic gene clusters that were absent in strains from the three non-pathogenic species. Furthermore, we identified over 2,000 orthologous proteins unique to A. flavus, which were enriched in the gene ontology categories of transmembrane transport and oxidoreductase activity. Despite the unique biosynthetic gene clusters and proteins in A. flavus, our chemical analyses showed few unique metabolites produced by any species. Temperature changes impacted metabolite production in all species, but we found a surprising lack of impact of salt on secondary metabolite production. We also found that strains of the same species varied widely in their virulence profiles, and that A. flavus strains were not more virulent than strains of the non-pathogenic species.
Conclusion:
Our work provides additional puzzle pieces in the study of A. flavus pathogenicity and its prevalence in human infections compared to its close, non-pathogenic relatives.
Abstract Number: 50
Conference Year: 2022
Link to conference website: https://aaam2022.org/
URL Conference abstract: