Vibrio cholerae biofilms: structure, function, regulation and role in infection

霍乱弧菌生物膜：结构、功能、调节和在感染中的作用

基本信息

批准号：
8786732
负责人：
Havva Fitnat Yildiz
金额：
$ 47.35万
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：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8786732
关键词：
Address Architecture Area Binding Biology Cells Cholera Clinical Communities Couples Developing Countries Development Disasters Disease Disease Outbreaks Drug Targeting Ecosystem Environment Environmental Risk Factor Epidemic Extracellular Matrix Face Family Feces Future Gene Cluster Genes Guanosine Monophosphate Habitats Human Image Infection Intestines Life Cycle Stages Location Maintenance Mechanics Mediating Microbe Microbial Biofilms Microscopy Modification Molecular Patients Phosphorylation Polysaccharides Process Production Property Proteins Proteolysis Regulation Regulon Resolution Role Sampling Structure Surface Testing Transcriptional Regulation Variant Vibrio Vibrio cholerae base combat genetic regulatory protein improved man member microbial community novel pathogen public health relevance sensor histidine kinase tool development transmission process

项目摘要

DESCRIPTION (provided by applicant): Vibrio cholerae causes the disease cholera and is a natural inhabitant of aquatic environments. Seasonal cholera outbreaks occur where the disease is endemic and can spread worldwide. V. cholerae's ability to form biofilms (i.e., matrix-enclosed, surface-associated communities) is crucial for its survival in aquatic habitats between epidemics and is advantageous for host-to-host transmission during epidemics. The objective of this proposal is to improve our understanding of biofilm matrix components, the mechanisms and regulation of biofilm formation, and their importance in the biology of V. cholerae. In Aim 1, we will focus on understanding how biofilm matrix proteins RbmA, RbmC and Bap1 function. We will determine the molecular basis of RbmA and VPS interactions and determine molecular determinants and consequences of RbmA proteolysis. We will test whether RbmC and Bap1 bind to VPS and identify regions important for their function. We will also determine how these proteins contribute to the mechanical properties of biofilms, as well as the location of each matrix component by super resolution microscopy. In Aim 2, we will determine the mechanism used by the regulatory proteins, VpsR and VpsT, in biofilm formation. We will identify sensor histidine kinases that phosphorylate VpsR, and determine phosphorylation dynamics of VpsR during biofilm development. We will also identify direct targets of VpsT and VpsR during biofilm formation and ascertain the contribution of VpsR and VpsT regulon members in V. cholerae transmission and dissemination into the environment. Clarifying the mechanisms of biofilm formation in V. cholerae will prove useful for the development of future strategies for controlling cholera epidemics, and facilitate identification of novel drug targets for combating the pathogen during infection.

描述（由申请人提供）：弧菌霍乱会引起疾病霍乱，是水生环境的自然居民。季节性的霍乱疫情发生在疾病流行并可能在全球范围内传播的地方。 V.霍乱形成生物膜的能力（即基质封闭的，与表面相关的群落）对于在流行病之间生存在水生栖息地中至关重要，并且在流行病期间对宿主到宿主传播是有利的。该提案的目的是提高我们对生物膜基质成分的理解，生物膜形成的机制和调节以及它们在V.霍乱生物学中的重要性。在AIM 1中，我们将专注于了解生物膜基质蛋白RBMA，RBMC和BAP1功能如何。我们将确定RBMA和VPS相互作用的分子基础，并确定RBMA蛋白水解的分子决定因素和后果。我们将测试RBMC和BAP1是否与VPS结合，并确定对其功能重要的区域。我们还将确定这些蛋白如何促进生物膜的机械性能，以及通过超级分辨率显微镜的每个矩阵分量的位置。在AIM 2中，我们将确定生物膜形成中调节蛋白，VPSR和VPST使用的机制。我们将确定磷酸化VPSR的传感器组氨酸激酶，并确定生物膜发育过程中VPSR的磷酸化动力学。我们还将在生物膜形成期间确定VPST和VPSR的直接靶标，并确定VPSR和VPST调节成员在V.霍乱弧菌传播和传播到环境中的贡献。阐明V.霍乱中生物膜形成的机制将被证明可用于制定未来控制的策略霍乱流行病，并促进了在感染过程中对抗病原体的新型药物靶标。