A genomic perspective on filamentous human pathogens: the Scedosporium case

Fungi are mostly investigated for their impact on agriculture, food and technology, however, these organisms are neglected, compared with bacteria, viruses and other eukaryotes. Moreover, new fungal patho- gens are expected to emerge with climate change and environmental pollution. Most human fungal pathogens are opportunistic: their ecological suc- cess is not dependent on host infection and their growth in the human body is occasional. However, the connection between extremophilic and pathogenic lifestyles is largely unexplored. Here, we focused on the genus Scedosporium (Microascaceae), a group of life-threatening fungi with outstanding degradative skills. Since the genomic data is fragmentary for the genus, we sequenced the genomes of S. auran- tiacum MUT6114 and S. minutisporum MUT6113, isolated from tan- nery wastewater and a Polyciclic Aromatic Hydrocarbons (PAH)-con- taminated soil, respectively. We characterized the publicly available Microascaceae genomes, most of which lacked annotation, and pro- vided the first comparative framework for this family. By comparing Microascaceae with other pathogenic and non-pathogenic ascomy- cetes, we found that quantitative traits are not sufficient to outline a common pathogenic genomic asset and that, from a phylogenomics perspective, there is a lack of convergence of putative pathogenicity traits. We investigated the role of point mutations and transposons insertions in pathogenicity and resistance to drugs, and found that these roles might have both ancient and recent roots. We also used RNA-seq to describe the response of the two isolates to the antifun- gal voriconazole, confirming the involvement of previously identified genomic traits. Our results highlight the strengths and limitations of genomics applied to opportunistic fungal human pathogens and the multifactoriality of pathogenicity and resistance to drugs. Finally, we discuss an evolutionary scenario where pressures other than anthrop- ic ones shaped pathogenic lifestyle in filamentous fungi.