Project C2

Regulation of Candida albicans virulence traits by protein kinases

Project Description

The opportunistic fungal pathogen Candida albicans continuously adapts to its environment both during mucosal colonisation of healthy persons and during infection of different tissues in immunocompromised patients. Reactions of the fungus to altered environmental conditions are, for example, changes in its morphology (e.g., from yeast to hyphal growth) or stress responses (e.g., adaptation to oxidative stress or nutrient limitation), which are accompanied by changes in gene expression. The reversible phosphorylation of proteins is a ubiquitous mechanism to trigger cellular reactions in response to extracellular and intracellular signals in all organisms. The aim of this project is a detailed functional analysis of all C. albicans protein kinases, which are responsible for the phosphorylation of effector proteins. By using comprehensive libraries of kinase-overexpressing strains and deletion mutants we aim at elucidating the role of specific kinases in the response to infection-relevant conditions and at identifying their target proteins. In addition, we will determine the changes in gene expression that are induced by the activation of individual kinases, their effects on the phenotype of C. albicans and the host’s immune response, and their importance for the fitness and virulence of C. albicans during colonisation and infection. These investigations will provide a comprehensive picture of the regulatory networks that enable the adaptation of the fungus during different stages of the pathogen-host interaction.

Principal Investigators

Prof. Dr. Joachim Morschhäuser
Prof. Dr. Joachim Morschhäuser

Institute for Molecular Infection Biology and Research Center for Infectious Diseases (ZINF)  

Julius Maximilians University Würzburg

joachim.morschhaeuser@mail.uni-wuerzburg.de

Dr. Slavena Vylkova
Dr. Slavena Vylkova

Center for Innovation Competence (ZIK) Septomics  
Research group Host Fungal Interfaces 

Friedrich Schiller University Jena

slavena.vylkova@leibniz-hki.de

Publications

Author Year Title Journal Links
Morschhäuser J 2016 The development of fluconazole resistance in Candida albicans - an example of microevolution of a fungal pathogen. J Microbiol 54: 192-201 PubMed
Ramírez-Zavala B, Mottola A, Haubenreißer J, Schneider S, Allert S, Brunke S, Ohlsen K, Hube B, Morschhäuser J 2017 The Snf1-activating kinase Sak1 is a key regulator of metabolic adaptation and in vivo fitness of Candida albicans. Mol Microbiol 104: 989-1007 PubMed
Hampe IAI, Friedman J, Edgerton M, Morschhäuser J 2017 An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses. PLoS Pathog 13:e1006655 PubMed