Deciphering the role of the Sch9 serine/threonine kinase in Scedosporium apiospermum.

Scedosporium apiospermum is an emerging opportunistic fungal pathogen, primarily affecting immunocompromised individuals. Notably, it ranks second among filamentous fungi infecting cystic fibrosis (CF) patients. Infections caused by S. apiospermum can range from localized infections to pulmonary colonization and invasive disseminated infections, often resulting in high mortality rates. This is largely attributed to the patient's clinical condition, limited diagnostic tools, and resistance to current antifungal therapies. Therefore, ongoing research is crucial to better understand the pathophysiology of these deep-seated fungal infections and to develop new strategies for early diagnosis and more effective antifungal treatments. In the present study, the Δsch9 gene, which encodes a major effector of the TOR pathway in fungi, was characterized. The deletion of sch9 significantly impaired S. apiospermum fitness under standard growth conditions and reduced hyphal development. Additionally, the Δsch9 mutant strain displayed increased sensitivity to oxidative stress and cell wall stress-inducing agents. The mutant strain showed an increase in germ tube formation during the early hours of growth, particularly under hypoxic and hypercapnic conditions. Furthermore, under standard growth conditions, the Δsch9 mutant strain exhibited a decrease in germ tube cell wall thickness compared to the Δku70 parent strain. Finally, disruption of Δsch9 affected the S. apiospermum ability to resist ingestion and killing by macrophages. Taken together, these findings suggest that Sch9 plays a crucial role in stress tolerance, morphogenesis, and host-pathogen interactions in S. apiospermum. Further studies are needed to explore Sch9 as a potential therapeutic target in the treatment of S. apiospermum infections.