Skn7 Regulates Response to Oxidative Stress in the Opportunistic Fungi Scedosporium apiospermum

The ability to survive and militate oxidative stress has received particular attention as one of the virulence factors of human pathogens. While underlying mechanisms have been largely studied for some fungi, those employed by the rising opportunistic fungal threat Scedosporium spp. are not fully understood yet. Previous transcriptomic studies helped identify the main oxidative stress-induced antioxidant enzymes in S. apiospermum. We therefore wanted to gain insight into regulators governing this response. We aimed to generate and characterize a knock-out mutant of S. apiospermum lacking the SKN7 gene, which encodes one of the main regulators of response to oxidative stress in fungi. The skn7Δ mutant was multifacetedly characterized on phenotypic and transcriptomic levels. Findings support pertinent roles of S. apiospermum Skn7 protein in protection against different types of oxidative stress, mainly cumene hydroperoxide and diamide. Skn7 was also protective against stress-induced accumulation of reactive oxygen species (ROS), as well as macrophage-mediated killing. This protection is likely mediated by the upregulation of genes encoding components of the thioredoxin and peroxiredoxin systems, which exhibit dependency on Skn7. Furthermore, we demonstrated a potential role of Skn7 in the synthesis of the hyphal cell wall. In conclusion, the response regulator Skn7 plays an essential role in protecting S. apiospermum against oxidative threat, whether generated by chemicals or by immune cells. Understanding the regulatory role of fungal Skn7 may help advance therapeutic strategies in combating fungal infections.