Surface adaptation in bacterial cells

项目总结/摘要 细菌常与固体表面紧密结合生长。人体组织如口腔， 肺、肠道和皮肤作为致病菌定植的表面， 负担尽管表面相关细菌对感染发展的重要性， 针对附着细胞的干预措施仍然很少。我的实验室试图了解 细菌如何在表面定居的机制。在表面生长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。近年来，能力 细菌识别与固体基质的接触已经成为表面适应的关键活化剂， 状态一种被称为鞭毛的分子机器参与了这些表面传感系统，但是 鞭毛允许细菌对物理接触作出反应一直难以表征。我们最近使用了一个 基因筛选，以确定几十个基因，使模型细菌新月柄杆菌作出反应， 表面接触。在我的实验室收集的初步数据表明，这些新的表面感应因素， 鞭毛到细胞的过程，这是目前的表面定殖模型所不包括的。目标 这里提出的工作之一是确定鞭毛如何协调细胞中的各种调节系统， 操纵面自适应我们将通过以下方式实现这一目标：（1）阐明趋化性和机械感应 交叉以促进表面反应和（2）确定表面接触如何影响细胞周期 进展这项研究利用了我的团队对表面遗传基础的新见解。 细菌细胞对物理接触的反应。这项工作的顺利完成将 鉴定用于治疗细菌感染的治疗靶标。

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.