Contact sensing and C. albicans-host interaction

描述（由申请人提供）：本研究项目调查了机会性真菌病原体白色念珠菌产生疾病的机制。本研究的长期目标是了解C。白色念珠菌细胞引起感染。 环境感知对于调节促进毒力的活动可能是重要的，例如C。白念珠菌细胞转化为侵入性丝状菌丝，其渗透到宿主组织中。在实验室条件下的入侵性研究表明，C。白色念珠菌细胞感觉到与半固体基质的接触，导致它们产生侵入性菌丝。一种质膜蛋白，它是侵入性生长所需的，以响应与琼脂培养基接触，并可能是一个传感器的接触已被确定。为了评估接触感测在感染期间对入侵的重要性，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将集中于分析缺乏几个组件的双重或三重突变体，这些组件对于感染动物模型的侵袭性是重要的。 在目标3中，将研究由感兴趣的质膜蛋白激活的信号通路。为了了解接触传感过程是如何发生的，Aim 4将寻求识别和表征与接触传感蛋白一起发挥作用的蛋白质。 这些研究将增加对C.白色念珠菌发病机制 公共卫生相关性：白色念珠菌是住院或免疫功能低下患者的重要病原体。感染C.白色念珠菌的特征在于生物体生长到其宿主的组织中。该研究项目旨在了解念珠菌的活动，这些活动是生物体生长到宿主组织所必需的，以便将来可能开发旨在阻止生长到组织中的治疗方法。

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.