Surface adaptation in bacterial cells

细菌细胞的表面适应

• 批准号: 10711843
• 负责人: David M. Hershey
• 金额: $ 38.21万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711843
• 关键词: Bacteria; Bacterial Infections; Caulobacter crescentus; Cell Cycle Progression; Cell physiology; Cells; Characteristics; Chemotaxis; Data; Development; Genes; Genetic; Genetic Screening; Goals; Health; Infection; Laboratories; Link; Lung; Modeling; Molecular Machines; Oral cavity; Physiological; Skin; Solid; Source; Surface; System; Therapeutic Intervention; Tissues; Work; chronic infection; human tissue; insight; mechanotransduction; novel; pathogenic bacteria; response; therapeutic target

PROJECT SUMMARY/ABSTRACT Bacteria often grow in close association with solid surfaces. Tissues of the human body such as the oral cavity, lungs, gut and skin serve as surfaces for colonization by pathogenic bacteria that cause a significant health burden. Despite the importance of surface-associated bacteria to the development of infections, therapeutic interventions that target attached cells remain scarce. My laboratory seeks to understand fundamental mechanisms of how bacteria colonize surfaces. Bacterial cells growing on surfaces display a variety of distinct physiological characteristics that we refer to collectively as the surface-adapted state. In recent years, the ability of bacteria to recognize contact with solid substrates has emerged as a critical activator of the surface-adapted state. A molecular machine called the flagellum participates in these surface sensing systems, but how the flagellum allows bacteria to respond to physical contact has been difficult to characterize. We recently used a genetic screen to identify dozens of genes that allow the model bacterium Caulobacter crescentus to respond to surface contact. Preliminary data collected in my laboratory show that these novel surface sensing factors link the flagellum to cellular process that are not encompassed by current models for surface colonization. The goal of the work proposed here is to define how the flagellum coordinates diverse regulatory systems in the cell to control surface adaptation. We will achieve this goal by (1) elucidating how chemotaxis and mechanosensing intersect to promote surface responses and (2) determining how surface contact influences cell cycle progression. The proposed studies leverage my group’s novel insights into the genetic basis for surface adaptation to define how bacterial cells respond to physical contact. Successful completion of this work will identify therapeutic targets for treating bacterial infections.

项目摘要/摘要 细菌通常与固体表面密切相关。人体的组织，例如口腔， 肺，肠道和皮肤充当致病细菌定植的表面，导致重大健康 负担。尽管表面相关细菌对感染的发展很重要，但治疗 靶向连接细胞的干预措施仍然稀缺。我的实验室试图了解基本 细菌如何定居表面的机制。生长在表面上的细菌细胞显示多种不同的 我们将物理特征集体称为表面适应状态。近年来，能力 识别与固体底物接触的细菌已成为表面适应的关键激活剂 状态。这些表面灵敏度系统中称为弗拉格的分子机器，但如何 Flagelum允许细菌对身体接触的反应很难表征。我们最近使用了 遗传筛选以鉴定数十种基因，这些基因允许模型细菌caulobacter crescentus对 表面接触。在我的实验室中收集的初步数据表明，这些新型的表面灵敏度因子链接 当前的表面定植模型所包含的鞭毛到细胞过程。目标 这里提出的工作是定义鞭毛如何坐在细胞中的潜水调节系统到 控制表面适应。我们将通过（1）阐明趋化性和机制如何实现这一目标 相交以促进表面反应和（2）确定表面接触如何影响细胞周期 进展。拟议的研究利用我小组的新见解对表面的遗传基础 适应以定义细菌细胞对身体接触的反应。成功完成这项工作将 确定治疗细菌感染的治疗靶标。

项目成果

A novel exopolysaccharide pathway from a freshwater Sphingomonas isolate.

来自淡水鞘氨醇单胞菌分离物的新型胞外多糖途径。

• DOI: 10.1101/2023.11.03.565537
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Goetsch,AlexandraG;Ufearo,Daniel;Keiser,Griffin;Heiss,Christian;Azadi,Parastoo;Hershey,DavidM
• 通讯作者: Hershey,DavidM