Vibrio cholerae c-diGMP signaling: motile to biofilm transition and transmission

霍乱弧菌 c-diGMP 信号传导：运动到生物膜的转变和传播

基本信息

批准号：
9280839
负责人：
Havva Fitnat Yildiz
金额：
$ 63.17万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9280839
关键词：
Address Affect Africa Alpha Cell Americas Area Asia Bacteria Behavior Biochemistry Biological Process Cell surface Cellular Structures Cholera Complex Critical Pathways Defect Developing Countries Dimerization Disasters Disease Disease Outbreaks Ecosystem Flagellin Genes Guanosine Monophosphate Habitats Hemagglutinin Human Individual Infection Intestines Investigation Lead Life Cycle Stages Life Style Link Mannose Methods Microbial Biofilms Molecular Motor Mutation Nucleotides Pathogenesis Periodicity Phase Phenotype Physiology Pilum Play Process Proteins Public Health Regulation Role Saline Second Messenger Systems Signal Transduction Signal Transduction Pathway Signaling Protein Solid Speed Structure Surface System Temperature Testing Translating Vibrio cholerae Virulence Work base cell motility combat diguanylate cyclase dimer experimental study improved man microorganism mutant pathogen phosphoric diester hydrolase protein function public health relevance receptor response transmission process

项目摘要

DESCRIPTION (provided by applicant): Vibrio cholerae, the causative agent of the disease cholera, is an important human pathogen that is an ongoing public health problem in regions of developing countries in the Americas, Asia, and Africa. In many bacteria including V. cholerae, cyclic dimeric guanosine monophosphate (c-diGMP) regulates motility, biofilm formation and virulence. We have a solid general understanding of the basic biochemistry of c-diGMP turnover and c-diGMP-dependent phenotypes, but critical questions remain. These include how does c-diGMP mechanistically control motile to biofilm life style switch in V. cholerae, how do environmental signals control c-di-GMP levels and biofilm formation in V. cholerae, and what are the consequences of c-diGMP signaling in the intestinal and aquatic and phases of V. cholerae life cycle. We will address these questions by focusing on two aims. In Aim 1, we will determine how specific key c-diGMP signaling proteins and cell surface structures act to control surface-associated motility, elucidate how motility status affects c-diGMP levels, and determine which c-diGMP proteins function together and which cellular proteins they target. In Aim 2, we will determine molecular mechanisms of environmental regulation of c-diGMP levels and analyze the impact of c-diGMP signaling proteins in V. cholerae aquatic and intestinal life cycles. Our studies will lead to a better understanding of c-diGMP signal transduction pathways that are critical for the life-cycle of V. cholerae and may, therefore, lead to new methods of combating this pathogen, as well as other disease-causing microorganisms that use c-diGMP signaling. This work will also contribute to the basic understanding of the newly emerging, ubiquitous, signal transduction network and, therefore, will be relevant to investigations of similar regulatory systems in a broad range of bacteria.

描述（由申请人提供）：该疾病霍乱的致病药物霍乱具型霍乱是一种重要的人类病原体，是美国，亚洲和非洲发展中国家地区的一个持续公共卫生问题。在许多细菌中，包括霍乱谷链球菌，环状二聚磷酸盐（C-DIGMP）调节运动性，生物膜形成和毒力。我们对C-DIGMP周转和C-DIGMP依赖性表型的基本生物化学有牢固的一般了解，但仍然存在关键问题。其中包括C-DIGMP如何机械地控制V. Cholerae中的生物膜生命风格，环境信号如何控制V.霍乱中的C-DI-GMP水平和生物膜形成，以及V. cholerae Life Cyce的肠道和水生和阶段中C-DIGMP信号的后果是什么。我们将通过关注两个目标来解决这些问题。在AIM 1中，我们将确定特定的C-DIGMP信号蛋白和细胞表面结构如何控制与表面相关的运动，阐明运动状态如何影响C-DIGMP水平，并确定哪种C-DIGMP蛋白在一起起作用以及它们靶向的细胞蛋白。在AIM 2中，我们将确定C-DIGMP水平环境调节的分子机制，并分析C-DIGMP信号传导蛋白在霍乱弧菌水生和肠子生命周期中的影响。我们的研究将使人们更好地了解C-DIGMP信号转导途径，这些途径对于V.霍乱的生命周期至关重要，因此可能导致对这种病原体的抗击以及其他使用C-DIGMP信号的微生物的新方法。这项工作还将有助于对新出现的，无处不在的信号转导网络的基本理解，因此将与对广泛细菌中类似调节系统的研究有关。