The Role of MAPK Signal Transduction Pathways in the Response to Oxidative Stress in the Fungal Pathogen Candida albicans: Implications in Virulence

Carmen      Herrero de Dios; Elvira      Roman; Rebeca      Alonso Monge; Jesus      Pla

Abstract

In recent years, Mitogen-Activated Protein Kinase (MAPK) pathways have emerged as major regulators of cellular physiology. In the fungal pathogen Candida albicans, three different MAPK pathways have been characterized in the last years. The HOG pathway is mainly a stress response pathway that is activated in response to osmotic and oxidative stress and also participates regulating other pathways. The SVG pathway (or mediated by the Cek1 MAPK) is involved in cell wall formation under vegetative and filamentous growth, while the Mkc1-mediated pathway is involved in cell wall integrity. Oxidative stress is one of the types of stress that every fungal cell has to face during colonization of the host, where the cell encounters both hypoxia niches (i.e. gut) and high concentrations of reactive oxygen species (upon challenge with immune cells). Two pathways have been shown to be activated in response to oxidative stress: the HOG pathway and the Mkc1-mediated pathway while the third, the Cek1 pathway is deactivated. The timing, kinetics, stimuli and functional responses generated upon oxidative stress differ among them; however, they have essential functional consequences that severely influence pathogenesis. MAPK pathways are, therefore, valuable targets to be explored in antifungal research.

Keywords: Candida albicans, MAP kinase, oxidative stress, virulence, filamentous growth, hypoxia niches, pathogeneces, transplantation, colonization, histidine kinase, hyper filamentous phenotype, mental-meditade formation, translocation, depresion