Examination of Genome-Wide Ortholog Variation in Clinical and Environmental Isolates of the Fungal Pathogen Aspergillus fumigatus

Author(s)

Horta, Maria Augusta C. ; Steenwyk, Jacob L. ; Mead, Matthew E. ; dos Santos, Luciano H. Braz ; Zhao, Shu ; Gibbons, John G. ; Marcet-Houben, Marina ; Gabaldon, Toni ; Rokas, Antonis ; Goldman, Gustavo H.

• Document type: Journal article
• Source: MBIO; v. 13, n. 4, p. 16-pg., 2022-06-29.

Abstract

Aspergillus fumigatus is a cosmopolitan species of fungus responsible for thousands of cases of invasive disease annually. Clinical and environmental isolates of A. fumigatus exhibit extensive phenotypic differences, including differences related to virulence and antifungal drug resistance. Aspergillus fumigatus is both an environmental saprobe and an opportunistic human fungal pathogen. Knowledge of genomic variation across A. fumigatus isolates is essential for understanding the evolution of pathogenicity, virulence, and resistance to antifungal drugs. Here, we investigated 206 A. fumigatus isolates (133 clinical and 73 environmental isolates), aiming to identify genes with variable presence across isolates and test whether this variation was related to the clinical or environmental origin of isolates. The PanOrtho genome of A. fumigatus consists of 13,085 ortholog groups, of which 7,773 (59.4%) are shared by all isolates (core groups) and 5,312 (40.6%) vary in their gene presence across isolates (accessory groups plus singletons). Despite differences in the distribution of orthologs across all isolates, no significant differences were observed among clinical versus environmental isolates when phylogeny was accounted for. Orthologs that differ in their distribution across isolates tend to occur at low frequency and/or be restricted to specific isolates; thus, the degree of genomic conservation between orthologs of A. fumigatus is high. These results suggest that differences in the distribution of orthologs within A. fumigatus cannot be associated with the clinical or environmental origin of isolates. IMPORTANCE Aspergillus fumigatus is a cosmopolitan species of fungus responsible for thousands of cases of invasive disease annually. Clinical and environmental isolates of A. fumigatus exhibit extensive phenotypic differences, including differences related to virulence and antifungal drug resistance. A comprehensive survey of the genomic diversity present in A. fumigatus and its relationship to the clinical or environmental origin of isolates can contribute to the prediction of the mechanisms of evolution and infection of the species. Our results suggest that there is no significant variation in ortholog distribution between clinical and environmental isolates when accounting for evolutionary history. The work supports the hypothesis that environmental and clinical isolates of A. fumigatus do not differ in their gene contents. (AU)

• FAPESP's process: 20/10536-9 - Organization and integration of large scale data to study the dynamics of expression of MAP kinases of the fungus Aspergillus fumigatus in diverse genetic and environmental conditions
• Grantee: Maria Augusta Crivelente Horta
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants