Contact sensing and C. albicans-host interaction

接触传感和白色念珠菌-宿主相互作用

• 批准号: 7782862
• 负责人: CAROL A. KUMAMOTO
• 金额: $ 41.25万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-07 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7782862
• 关键词: Address; Adherence; Affect; Agar; Animal Disease Models; Animal Model; Antifungal Agents; Attenuated; Behavior; Binding; Candida; Candida albicans; Caspofungin; Cell Wall; Cell membrane; Cells; Congo Red; Disease; Disseminated candidiasis; Environment; Exhibits; Future; Genes; Goals; Growth; Hyphae; Immunocompromised Host; Infection; Intravenous; Laboratories; Link; Mediating; Membrane Proteins; Mitogen-Activated Protein Kinases; Modeling; Normal Cell; Oral; Oral candidiasis; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Phosphotransferases; Play; Predisposition; Process; Proteins; Regulation; Research; Research Project Grants; Resistance; Role; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Solid; Surface; Testing; Tissues; Virulence; Work; base; drug development; glucan synthase; innovation; interest; mutant; novel; pathogen; protein function; public health relevance; response; sensor; transcription factor

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.

描述（由申请人提供）：该研究项目研究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。 环境传感可能对于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性丝状菌丝并渗透到宿主组织中的能力。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。一种质膜蛋白已被表征，该蛋白是响应与琼脂培养基接触而进行侵入性生长所必需的，并且可能是接触传感器。为了评估接触传感对于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（目标 1）。 初步研究表明其他质膜蛋白也参与接触传感。目标 2 将重点分析缺乏对感染动物模型的侵袭性很重要的几种成分的双重或三重突变体。 在目标 3 中，将研究由感兴趣的质膜蛋白激活的信号传导途径。为了了解接触传感过程是如何发生的，目标 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。 这些研究将增加对白色念珠菌发病机制中重要调节机制的理解。 公共卫生相关性：白色念珠菌是住院患者或免疫功能低下患者的重要病原体。白色念珠菌感染的特征是该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在宿主组织中生长所必需的活性，以便开发出旨在阻止其生长到组织中的未来疗法。