Contact sensing and C. albicans-host interaction

描述（由申请人提供）：本研究项目探讨机会性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如何引起感染。环境感知可能对促进毒力的活动的调节很重要，例如白色念珠菌细胞转化为侵入性丝状菌丝的能力，这种能力可以渗透到宿主组织中。在实验室条件下的侵袭性研究表明，白色念珠菌细胞感知与半固体基质的接触，导致它们产生侵袭性菌丝。一种质膜蛋白是侵入性生长所需要的反应与琼脂培养基的接触，可能是一种接触传感器。为了评估接触传感在感染期间入侵的重要性，将在几种感染动物模型中研究缺乏传感器的突变体（目的1）。初步研究表明，其他质膜蛋白也参与接触传感。目标2将侧重于分析缺乏对动物感染模型侵袭性重要成分的双或三重突变体。在Aim 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起作用的蛋白质。这些研究将增加对白色念珠菌发病机制中重要的调控机制的理解。

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. PUBLIC HEALTH RELEVANCE: Candida albicans is an important pathogen of hospitalized or otherwise immunocompromised patients. Infection by C. albicans is characterized by growth of the organism into the tissues of its host. This research project seeks to understand Candida activities that are necessary for the growth of the organism into host tissue so that future therapies aimed at blocking growth into tissue might be developed.