Contact sensing and C. albicans-host interaction

描述(由申请人提供)：这项研究项目调查了机会真菌病原体白色念珠菌产生疾病的机制。这项研究的长期目标是了解白色念珠菌细胞是如何导致感染的。环境感知可能对调节促进毒力的活动很重要，例如白色念珠菌细胞转化为侵入宿主组织的丝状菌丝的能力。在实验室条件下对侵袭性的研究表明，白色念珠菌细胞感觉到与半固体基质的接触，导致它们产生侵袭性菌丝。一种质膜蛋白在与琼脂介质接触后的侵袭性生长中所需的，可能是接触的传感器已经被表征。为了评估在感染过程中接触感应对入侵的重要性，将在几种感染动物模型中研究缺乏接触感应的突变体(目标1)。初步研究表明，其他质膜蛋白也参与了接触感应。目标2将重点分析在动物感染模型中缺少对侵袭性重要的几种成分的双或三重突变体。在目标3中，将研究由感兴趣的质膜蛋白激活的信号通路。为了了解接触感应过程是如何发生的，Aim 4将寻求识别和表征与接触感应蛋白一起发挥功能的蛋白质。这些研究将增加对白色念珠菌致病中重要的调节机制的理解。

DESCRIPTION (provided by applicant): This research project investigates the mechanisms used by the opportunistic fungal pathogen, Candida albicans to produce disease. The long term goal of this research is to understand how C. albicans cells cause infection. Environmental sensing is likely to be important for regulation of activities that promote virulence, such as the ability of C. albicans cells to convert into invasive filamentous hyphae, which penetrate into host tissue. Studies of invasiveness under laboratory conditions have shown that C. albicans cells sense contact with a semi-solid matrix, causing them to produce invasive hyphae. A plasma membrane protein that is needed for invasive growth in response to contact with agar medium and may be a sensor of contact has been characterized. To evaluate the importance of contact sensing for invasion during infection, a mutant lacking the sensor will be studied in several animal models of infection (Aim 1). Preliminary studies suggest that other plasma membrane proteins also participate in contact sensing. Aim 2 will focus on analyzing double or triple mutants lacking several components that are important for invasiveness in animal models of infection. In Aim 3, signaling pathways that are activated by the plasma membrane proteins of interest will be investigated. To understand how the contact sensing process takes place, Aim 4 will seek to identify and characterize proteins that function with the contact sensing protein. These studies will increase the understanding of regulatory mechanisms that are important in C. albicans pathogenesis.