CO2 Adaptation in Candida glabrata und ihre Rolle in der Pathogen Wirt Interaktion

点击翻译按钮获取中文摘要

CO2 is a central environmental signal and critical for fungal metabolism and growth. High levels of CO2 are linked to regulation of virulence determinants in fungal pathogens including filamentation in C. albicans and capsule expression in C. neoformans. Like other organisms, fungal pathogens respond to alternating CO2 concentrations with a complex regulatory process. On a molecular level CO2 adap-tation involves activation of the multi-sensor adenylyl cyclase (AC), and additionally an AC-independent CO2 sensing pathway. The central transcriptional regulator of the latter, Rca1p, was re-cently identified by Prof. Mühlschlegel in collaboration with the applicant. In comparison to cAMP mediated CO2 sensing hardly anything is known about AC-independent CO2 sensing involving Rca1p. Unraveling of this alternate cascade, which is conserved in yeasts, is the central aim of the current application. To achieve this aim we will not only investigate CO2 sensing in the fungal pathogen Can-dida glabrata but also make use of the unrivaled genomic resources available for the closely related model yeast Saccharomyces cerevisiae, including completed knock-out libraries, possibility of syn-thetic-lethal screens, high-throughput transformation and multiple reporter systems. Previous work by the applicant has shown that CO2 sensing in C. glabrata is also of direct relevance for the interaction with the immune system. Thus, characterization of this novel aspect will be integrated into the further analysis of CO2 signaling. The aim of this project is the further elucidation of Rca1-signaling in CO2-Adaptation and an analysis of its role in pathogen-host interaction.