Characterizing the Pathogenic, Genomic, and Chemical Traits of Aspergillus fischeri , a Close Relative of the Major Human Fungal Pathogen Aspergillus fumigatus

Abstract

Aspergillus fumigatus is the primary cause of aspergillosis, a devastating ensemble of diseases associated with severe morbidity and mortality worldwide. A. fischeri is a close relative of A. fumigatus but is not generally observed to cause human disease. To gain insights into the underlying causes of this remarkable difference in pathogenicity, we compared two representative strains (one from each species) for a range of pathogenesis-relevant biological and chemical characteristics. We found that disease progression in multiple A. fischeri mouse models was slower and caused less mortality than A. fumigatus. Remarkably, the observed differences between A. fischeri and A. fumigatus strains examined here closely resembled those previously described for two commonly studied A. fumigatus strains, AF293 and CEA10. A. fischeri and A. fumigatus exhibited different growth profiles when placed in a range of stress-inducing conditions encountered during infection, such as low levels of oxygen and the presence of chemicals that induce the production of reactive oxygen species. We also found that the vast majority of A. fumigatus genes known to be involved in virulence are conserved in A. fischeri, whereas the two species differ significantly in their secondary metabolic pathways. These similarities and differences that we report here are the first step toward understanding the evolutionary origin of a major fungal pathogen.

Evolving moldy murderers: Aspergillus section Fumigati as a model for studying the repeated evolution of fungal pathogenicity

“…Support for the role of genetic differences in contributing to the observed spectrum of pathogenicity is provided by the numerous traits, and their underlying genes and pathways, that are required for pathogenicity in A. fumigatus [2,19,20,37] and have been found to exhibit substantial genetic and phenotypic diversity among section Fumigati species. These traits include thermotolerance, the ability to respond to multiple environmental stresses, including antifungal drugs, and the capacity to biosynthesize a range of structurally diverse secondary metabolites [14,30,38,39].…”

“…For the trait reconstruction inference, Biosafety Level (BSL) 2 organisms were considered pathogenic and BSL1 organisms or organisms that so far lack BSL labelling were considered non-pathogenic; these transitions to a pathogenic lifestyle (i.e., from BSL1 to BSL2) are labelled by red bars on the figure. Note that clinical isolates from humans or other mammals from a few additional species in the section have been identified [10,28]; this handful includes relatively newly described species that some authors consider to have pathogenic potential (e.g., Aspergillus novofumigatus [29]) as well as organisms thought to be on the non-pathogenic end of the spectrum (e.g., A. fischeri [30,31]). The phylogeny of the section was redrawn from Hubka et al [16].…”

“…For example, the conserved pathogenicity model would predict that pathogenicity stems from the action of conserved genetic elements, suggesting that known genetic determinants of virulence in A. fumigatus [40] would be great candidates for involvement in virulence in other pathogenic Aspergillus species. It is the adoption of the conserved pathogenicity model that underlies recent examinations of the degree to which genetic elements known to contribute to A. fumigatus pathogenicity are conserved in other species [29,30,41]. In contrast, the species-specific model would predict the opposite, namely that the genetic determinants of virulence are unique to each pathogen, suggesting that extrapolations of knowledge on virulence mechanisms from one pathogenic species to another would be futile.…”

“…In contrast, the species-specific model would predict the opposite, namely that the genetic determinants of virulence are unique to each pathogen, suggesting that extrapolations of knowledge on virulence mechanisms from one pathogenic species to another would be futile. Genomic comparisons between the major pathogen A. fumigatus and its close non-pathogenic relative A. fischeri [30,31] as well as broad comparisons of select species across the genus [29,41] have begun to shed light on the validity of, and provide support for, both of these models.…”

Comparative genome and transcriptome analyses revealing interspecies variations in the expression of fungal biosynthetic gene clusters

“…This is in sharp contrast to primary metabolic genes, which are 7.5%–15.4% species-specific (7). Comparisons between more closely related species using A. fumigatus and Neosartorya fischeri or Aspergillus novofumigatus , which all belong to Aspergillus section Fumigati revealed that 30.3% or 70.5% of A. fumigatus SM genes were shared, respectively (8,9). Comprehensive genomic studies in Aspergillus sections Nigri and Flavi also showed overlaps of SM genes at specific rates.…”