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

光滑念珠菌的二氧化碳适应及其在病原体-宿主相互作用中的作用

• 批准号: 233815546
• 负责人: Professor Dr. Oliver Kurzai
• 金额: --
• 依托单位: Institut für Hygiene und Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233815546?language=en
• 关键词: CO2; Adaptation; Candida; glabrata; und

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.

二氧化碳是一种重要的环境信号，对真菌的代谢和生长至关重要。高水平的二氧化碳与真菌病原体的毒力决定因素的调节有关，包括白色念珠菌的丝状和新生念珠菌的荚膜表达。像其他生物一样，真菌病原体对交替的二氧化碳浓度有一个复杂的调节过程。在分子水平上，二氧化碳适应包括多传感器腺苷酸环化酶（AC）的激活，以及一个与AC无关的二氧化碳感知途径。后者的中心转录调控因子Rca1p，最近由m<s:1> hlschlegel教授与申请人合作确定。与cAMP介导的CO2传感相比，我们对涉及Rca1p的交流非依赖性CO2传感几乎一无所知。解开这个在酵母中保存的交替级联，是当前应用的中心目标。为了实现这一目标，我们不仅将研究真菌病原体candidida glabrata的CO2传感，还将利用密切相关的模式酵母Saccharomyces cerevisiae的无与伦比的基因组资源，包括完整的敲除文库、合成致死筛选的可能性、高通量转化和多个报告系统。申请人之前的工作表明，C. glabrata中的CO2传感也与免疫系统的相互作用直接相关。因此，这一新方面的表征将被整合到二氧化碳信号的进一步分析中。本项目的目的是进一步阐明rca1信号在co2适应中的作用，并分析其在病原体-宿主相互作用中的作用。