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：
8659337
负责人：
CAROL A. KUMAMOTO
金额：
$ 40.84万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-07 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8659337
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 response sensor transcription factor

项目摘要

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.

描述（由申请人提供）：该研究项目研究了机会性真菌病原体，白色念珠菌生产疾病的机制。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，将在几种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将重点放在分析缺少几个组成部分的双重突变体或三重突变体上，对于动物感染模型中的侵入性很重要。在AIM 3中，将研究被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的发生方式，AIM 4将寻求识别和表征与接触传感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理重要的调节机制的理解。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inflammation and gastrointestinal Candida colonization.

DOI：
10.1016/j.mib.2011.07.015
发表时间：
2011-08
期刊：
CURRENT OPINION IN MICROBIOLOGY
影响因子：
5.4
作者：
Kumamoto, Carol A.
通讯作者：
Kumamoto, Carol A.

Functional importance of the DNA binding activity of Candida albicans Czf1p.

DOI：
10.1371/journal.pone.0039624
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Petrovska I;Kumamoto CA
通讯作者：
Kumamoto CA

Experimental annotation of the human pathogen Candida albicans coding and noncoding transcribed regions using high-resolution tiling arrays.

DOI：
10.1186/gb-2010-11-7-r71
发表时间：
2010
期刊：
Genome biology
影响因子：
12.3
作者：
Sellam A;Hogues H;Askew C;Tebbji F;van Het Hoog M;Lavoie H;Kumamoto CA;Whiteway M;Nantel A
通讯作者：
Nantel A