Project 170495

Pathogenic E.coli infections are a serious global health concern. During their disease processes, these organisms remain outside of host cells and inject a multitude of pathogenic proteins to commandeer normal cellular functions. A characteristic feature of these diseases involves the generation of host cell protrusions beneath the attached bacteria that results in these microbes rising off the natural surface of the cell onto E.coli generated structures called, pedestals. Surprisingly, I recently found that clathrin, a protein known to internalize particles and other bacteria into cells, is an essential component of pedestals and is required for their generation, thus providing a previously unknown function of this protein. In order to understand the mechanisms involved in the non-internalization functions of clathrin, I will examine the subversion strategies that pathogenic E.coli use to avoid clathrin-based internalization in order to remain extracellular. In addition to understanding the methods used by these bacteria to generate disease, this work will also provide insight into the general mechanisms of controlling particle internalization thus allowing for the design of therapeutics.