Surface adaptation in bacterial cells

项目总结/文摘

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.