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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：
10624392
负责人：
Havva Fitnat Yildiz
金额：
$ 53.35万
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 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624392
关键词：
3-Dimensional Acute Diarrhea Address Architecture Bacteria Bacterial Adhesins Binding Biogenesis Biological Models Cells Chitin Cholera Clinical Communities Development Disease Disease Outbreaks Disease Progression Ecosystem Environment Environmental Impact Epidemic Extracellular Matrix Extracellular Protein Factor V Gene Cluster Growth Habitats Human Image Imaging Techniques Industrialization Infant Infection Ingestion Intervention Intestines Life Style Lipids Location Mediating Membrane Membrane Proteins Microbe Microbial Biofilms Molecular Mucins Optics Organism Pattern Play Polysaccharides Production Proteins Proteome Public Health Regulation Research Role Route Seasons Small Intestines Spatial Distribution Structure Surface Testing Tissues Vesicle Vibrio Vibrio cholerae Vibrio cholerae infection combat design diarrheal disease enteric infection human pathogen improved inhibitor insight interdisciplinary approach intestinal villi microbial community mouse model new therapeutic target pathogen pathogenic bacteria predictive tools preservation therapy development tool transmission process

项目摘要

SUMMARY 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, extracellular matrix-enclosed, surface-associated microbial 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 elucidate the molecular mechanisms of biofilm formation and biofilm-mediated hyperinfectivity. In Aim 1, we will focus on understanding the mechanisms of V. cholerae biofilm matrix biogenesis. We recently characterized the V. cholerae biofilm matrix proteome and will determine the role of a prioritized set of the newly identified proteins in matrix biogenesis and function. We will also specifically analyze how biofilm biogenesis is impacted by bacterial outer membrane vesicles, which we found to be associated with the biofilm matrix, and identify the molecular determinants and the consequences of interactions between the identified exopolysaccharides, proteins, and lipid constituents of the biofilm matrix. In Aim 2, we will determine the impact of environmental and host surfaces on biofilm formation and biofilm hyperinfectivity. Specifically, we will determine how newly identified V. cholerae adhesins impact biofilm formation on chitinous surfaces, and identify the molecular determinants of biofilm formation on chitinous surfaces. To gain insight into biofilm hyperinfectivity, we will analyze the molecular mechanisms underlying V. cholerae interaction with intestinal mucin, determine the spatial and temporal colonization dynamics of planktonic versus biofilm-grown cells, and evaluate the impact of biofilm matrix components on the colonization of the small intestine. A better understanding of the molecular principles of matrix biogenesis and biofilm hyperinfectivity will allow us to identify targets for the development of inhibitors of V. cholerae infection and transmission.

总结霍乱弧菌引起霍乱，是水生环境的天然居民。季节性霍乱在疾病流行的地方发生暴发，并可在世界范围内传播。霍乱弧菌形成生物膜的能力，细胞外基质封闭，表面相关的微生物群落，是至关重要的，它的生存在水生在流行病之间的栖息地，并有利于在流行病期间宿主到宿主的传播。客观这一建议的目的是阐明生物膜形成和生物膜介导的分子机制，高传染性在目标1中，我们将重点了解霍乱弧菌生物膜基质的机制，生物起源。我们最近对霍乱弧菌生物膜基质蛋白质组进行了表征，并将确定一个蛋白质组的作用。在基质生物发生和功能中新鉴定的蛋白质的优先级设置。我们还将具体分析细菌外膜囊泡如何影响生物膜的生物发生，我们发现这与生物膜基质，并确定分子决定因素和生物膜基质之间相互作用的后果。鉴定了生物膜基质的胞外多糖、蛋白质和脂质成分。在目标2中，我们将确定环境和宿主表面对生物膜形成和生物膜高感染性的影响。我们特别将确定新鉴定的霍乱弧菌粘附素如何影响几丁质表面上的生物膜形成，确定几丁质表面生物膜形成的分子决定因素。为了深入了解生物膜高感染性，我们将分析潜在的分子机制V.霍乱相互作用与肠道粘蛋白，确定粘附细胞与生物膜生长细胞的空间和时间定殖动力学，以及评价生物膜基质组分对小肠定殖的影响。更好的了解基质生物发生和生物膜高感染性的分子原理将使我们能够识别开发霍乱弧菌感染和传播抑制剂的靶点。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

VxrB Influences Antagonism within Biofilms by Controlling Competition through Extracellular Matrix Production and Type 6 Secretion.

DOI：
10.1128/mbio.01885-22
发表时间：
2022-08-30
期刊：
mBio
影响因子：
6.4
作者：
通讯作者：

CdiA promotes receptor-independent intercellular adhesion.

DOI：
10.1111/mmi.13114
发表时间：
2015-10
期刊：
Molecular microbiology
影响因子：
3.6
作者：
Ruhe ZC;Townsley L;Wallace AB;King A;Van der Woude MW;Low DA;Yildiz FH;Hayes CS
通讯作者：
Hayes CS

Living in the matrix: assembly and control of Vibrio cholerae biofilms.

DOI：
10.1038/nrmicro3433
发表时间：
2015-05
期刊：
Nature reviews. Microbiology
影响因子：
0
作者：
Teschler JK;Zamorano-Sánchez D;Utada AS;Warner CJ;Wong GC;Linington RG;Yildiz FH
通讯作者：
Yildiz FH

The ins and outs of cyclic di-GMP signaling in Vibrio cholerae.