Surface adaptation in bacterial cells

项目摘要/摘要 细菌常常与固体表面紧密结合生长。人体组织，如口腔， 肺、肠道和皮肤是致病细菌定植的表面，致病细菌对人体健康有重大影响。 负担。尽管表面相关细菌对感染的发展很重要，但治疗 针对附着细胞的干预措施仍然很少。我的实验室试图了解基本原理 细菌如何在表面定植的机制。生长在表面的细菌细胞显示出各种不同的 我们统称为表面适应状态的生理特征。近几年来，能力 识别与固体底物接触的细菌已经成为适应表面的关键激活剂 州政府。一种名为鞭毛的分子机器参与了这些表面传感系统，但 鞭毛允许细菌对身体接触做出反应一直很难表征。我们最近使用了一个 基因筛查以确定数十个允许模式细菌新月弯杆菌对其产生反应的基因 表面接触。在我的实验室收集的初步数据表明，这些新的表面传感因素 鞭毛到细胞的过程，这是目前的表面定植模型所不包括的。目标是 这里提出的工作之一是定义鞭毛如何协调细胞中的不同调节系统 操纵面自适应。我们将通过(1)阐明趋化性和机械感觉如何 交集以促进表面反应和(2)确定表面接触如何影响细胞周期 进步。拟议的研究利用了我的团队对表面的遗传基础的新见解 适应以定义细菌细胞如何对身体接触做出反应。这项工作的圆满完成将 确定治疗细菌感染的治疗目标。

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.