Regulatory mechanism of novel host-relevant biofilm formation protein in non-Cholera Vibrio species

非霍乱弧菌中新型宿主相关生物膜形成蛋白的调节机制

• 批准号: 10505474
• 负责人: Morgan Eilise Milton
• 金额: $ 15.68万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-02 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10505474
• 关键词: Address; Bacillus subtilis; Bacteria; Bacterial Infections; Binding; Biochemical; Biophysics; Communities; Complex; Data; Disease; Drug resistance; Environment; Extracellular Matrix; Food Poisoning; Food Safety; Funding; Future; Gene Expression; Genetic; Genetic Transcription; Goals; Health; Homologous Gene; Human; Infection; K22 Award; Knowledge; Microbial Biofilms; Molecular; Outcome; Pathogenesis; Pathway interactions; Phosphorylation; Play; Polysaccharides; Positioning Attribute; Process; Production; Protein Family; Proteins; Public Health; Publications; Regulation; Regulatory Pathway; Research; Research Personnel; Resources; Role; Sigma Factor; Signal Pathway; Structure; Subgroup; Surface; Symbiosis; System; Techniques; Tertiary Protein Structure; Therapeutic Intervention; United States; Vibrio; Vibrio Infections; Vibrio fischeri; Vibrio parahaemolyticus; Vibrio vulnificus; Virulence; Work; Wound Infection; antagonist; bacterial community; bacterial resistance; experimental study; genetic analysis; genetic approach; genetic regulatory protein; host-associated biofilms; human pathogen; innovation; insight; model organism; novel; nucleoside triphosphatase; protein complex; protein protein interaction; protein structure; response; sulfate transporter

PROJECT SUMMARY/ABSTRACT Non-cholera Vibrio (NCV) species represent a notable and increasing threat to human health and food safety. The biofilms formed by Vibrio species are robust and highly relevant to host infection. Biofilms are tightly regulated communities of matrix-associated bacteria and are a major component of bacterial pathogenesis including drug resistance. Since an estimated 75% of bacterial infections involve biofilms, it is crucial to better understand how biofilms are formed. In this application, I propose to elucidate the molecular mechanism of an unusual regulatory protein necessary for controlling NCV biofilm formation. This protein is conserved in NCVs and controls the production of symbiosis polysaccharide (Syp), a component of the biofilm matrix involved in host infection. Based on preliminary findings, this protein has an atypical mode of action compared to well characterized homologs. My fundamental hypothesis is that this NCV biofilm regulator protein uses a novel mechanism to control biofilm formation and will challenge our current understanding of this family of proteins. My hypothesis will be addressed through two specific aims: 1) probing the protein’s function using biochemical and structural characterization studies, and 2) uncovering its position in the regulatory network by identifying binding partners. The proposed research is innovative because it focuses on a system that is crucial for biofilm formation, and to date, the system has only been investigated using cellular and genetic approaches. The structure-function approach proposed here will provide essential information needed to fill our knowledge gaps. The project is significant because it will provide a deeper understanding of the regulation of host-associated biofilms from the rising threat of NCV infection. Ultimately, the work proposed will answer key questions related to the molecular mechanisms of a protein within a critical and conserved pathway that regulates host-relevant biofilms. Support from this K22 award will facilitate my transition to an independent investigator by providing me with resources to generate data and publications that will strengthen my competitiveness for future funding.

项目摘要/摘要 非胆碱弧菌（NCV）物种代表着对人类健康和食品安全的著名且日益增加的威胁。 由弧菌形成的生物膜与宿主感染相关，高度相关。生物膜紧密 基质相关细菌的受调节群落是细菌发病机理的主要组成部分 包括耐药性。由于估计有75％的细菌感染涉及生物膜，因此至关重要 了解生物膜的形成方式。在此应用中，我建议阐明 控制NCV生物膜形成所需的异常调节蛋白。该蛋白在NCV中保守 并控制共生多糖（SYP）的产生，这是与生物膜基质的组成部分 宿主感染。基于初步发现，该蛋白质具有非典型的作用方式 特征同源物。我的基本假设是，这种NCV生物膜调节蛋白使用了一种新颖 控制生物膜形成的机制，并将挑战我们当前对这种蛋白质家族的理解。 我的假设将通过两个具体目的解决：1）使用生化探测蛋白质的功能 和结构表征研究，以及2）通过识别识别其在调节网络中的位置 约束伙伴。拟议的研究具有创新性，因为它专注于对生物膜至关重要的系统 形成，迄今为止，该系统仅使用细胞和遗传方法研究。 这里提出的结构功能方法将提供填补我们的知识差距所需的基本信息。 该项目很重要，因为它将对宿主相关的调节有更深入的了解 NCV感染威胁不断上升​​的生物膜。最终，提议的工作将回答与关键问题有关 在关键且构成的途径中，蛋白质的分子机制调节宿主相关的途径 生物膜。这项K22奖的支持将通过向我提供给我向独立调查员的过渡 利用资源生成数据和出版物，可以增强我对未来资金的竞争力。