Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V33
Höfundar / Authors: Sebastian Schruefer (1), Astrid Thomas (1), Anna Vincek (1), Anja Wolf (1) and Frank Ebel (1)
Starfsvettvangur / Affiliations: 1. LMU Munich, Institute for Infectious Diseases and Zoonoses, Chair of Bacteriology and Mycology, Oberschleissheim, Germany
Kynnir / Presenter: Sebastian Schruefer
In the pathogenic mold Aspergillus fumigatus the high osmolarity glycerol (HOG) pathway plays a crucial role in stress adaptation under hyperosmotic conditions. Moreover, it represents a promising antifungal drug target, as small molecules such as fludioxonil induce its lethal hyperactivation. A detailed understanding of the regulatory mechanisms of this pathway is therefore essential. Our previous work identified the hybrid histidine kinase TcsC as essential for the adaptation to osmotic stress and, in co-operation with the downstream response regulator (RR) Skn7, it is also a key mediator of the fludioxonil-induced cell death. TcsC initiates the multistep phosphorelay (MSPR), which involves the phosphotransfer protein Ypd1 and results in the absence of stress in phosphorylation of the RRs SskA and Skn7. Activation of Skn7 increases intracellular pressure and destabilizes the fungal cell wall, ultimately leading to cell lysis. In this study, we investigated how the MSPR controls the activity of the HOG pathway in the presence and absence of stress. Expression of mutated tcsC variants in a ∆tcsC strain enabled us to study the impact of different mutations and the response to osmotic stress and fludioxonil. The spatio-temporal dynamics of the signaling cascade was analyzed using different GFP fusion proteins. The resulting data lay the foundation for a deeper understanding of the MSPR and its role in antifungal activity of fludioxonil and stress response in A. fumigatus.