Contact sensing and C. albicans-host interaction

接触传感和白色念珠菌-宿主相互作用

基本信息

批准号：
7811667
负责人：
CAROL A. KUMAMOTO
金额：
$ 41.23万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-08 至 2010-06-06
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7811667
关键词：
Acquired Immunodeficiency Syndrome Adherence Affect Agar Animal Disease Models Animal Model Anti-Bacterial Agents Antifungal Agents Bacterial Typing Behavior Binding Candida Candida albicans Candidiasis Caspofungin Cell Wall Cell membrane Cells Defect Development Disease Environment Family Future G-Protein-Coupled Receptors GTP-Binding Proteins Genes Goals Growth Hyphae Immunocompromised Host Immunosuppression Infection Intestines Intravenous Invaded Laboratories Membrane Proteins Modeling Morphogenesis Normal Cell Nosocomial Infections Oral Oral candidiasis Organism Pathogenesis Pathogenicity Pathway interactions Patients Pharmaceutical Preparations Phenotype Phosphotransferases Play Predisposing Factor Predisposition Process Proteins Regulation Research Research Project Grants Role Signal Pathway Signal Transduction Signal Transduction Pathway Solid Surface Systemic infection Testing Tissues Virulence Virulent Work base drug development experience fungus innovation mimicry mouse model mutant novel pathogen response sensor transcription factor

项目摘要

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 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 more than one component that promotes invasiveness. The phenotypes of such mutants during laboratory agar invasion will be studied. To understand how the contact sensing process takes place, Aim 3 will seek to identify and characterize binding partners that function with the contact sensing protein. These studies will increase the understanding of regulatory mechanisms that are important in C. albicans pathogenesis.

该研究项目调查了机会性真菌病原体（念珠菌白色念珠菌）使用的机制。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。环境传感对于调节促进毒力的活性可能很重要，例如白色念珠菌细胞转化为侵入性丝状菌丝的能力，这些菌丝渗透到宿主组织中。实验室条件下的侵入性研究表明，白色念珠菌细胞与半固体基质接触，导致它们产生侵入性菌丝。具有侵入性生长需要的质膜蛋白，以响应与琼脂培养基接触，并且可能是接触传感器。为了评估接触感应在感染过程中侵袭的重要性，将在感染动物模型中研究缺乏传感器的突变体（AIM 1）。初步研究表明，其他质膜蛋白也参与接触感应。 AIM 2将集中于分析缺乏促进侵入性的多个组成部分的双重突变体或三重突变体。将研究实验室琼脂入侵期间此类突变体的表型。为了了解接触传感过程的发生方式，AIM 3将寻求识别和表征与接触感应蛋白一起起作用的结合伴侣。这些研究将增加对白色念珠菌发病机理重要的调节机制的理解。