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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：
10407485
负责人：
Havva Fitnat Yildiz
金额：
$ 54.53万
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/10407485
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 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 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.

摘要霍乱弧菌导致霍乱，是水环境中的自然居住者。季节性霍乱暴发发生在疾病流行的地方，并可在全球范围内传播。霍乱弧菌形成生物膜的能力，细胞外基质封闭的、表面相关的微生物群落对其在水生环境中的生存至关重要流行病之间的栖息地，并有利于在流行期间从宿主传播到宿主。目标是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。高度传染性。在目标1中，我们将重点了解霍乱弧菌生物被膜基质的机制。生物发生学。我们最近鉴定了霍乱弧菌生物膜基质蛋白质组，并将确定一个在基质生物发生和功能中新发现的一组优先蛋白质。我们还将具体分析细菌外膜小泡对生物膜生物发生的影响生物膜基质，并确定分子决定因素和相互作用的后果鉴定生物膜基质的胞外多糖、蛋白质和脂类成分。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。具体来说，我们将确定新发现的霍乱弧菌粘附素如何影响几丁质表面的生物膜形成，以及确定几丁质表面生物膜形成的分子决定因素。深入了解生物膜高传染性，我们将分析霍乱弧菌与肠道相互作用的分子机制粘蛋白，决定浮游细胞与生物膜生长细胞的空间和时间定植动态，以及评估生物膜基质成分对小肠定植的影响。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霍乱弧菌感染和传播抑制剂的开发目标。