Spectrin is a crucial component of EPEC pedestals

Abstract

Enteropathogenic E.coli (EPEC) is one of the main pathogens contributing to roughly 2 million diarrhea related child deaths worldwide each year. Upon ingestion of contaminated food or water, EPEC colonize the intestinal tracts of their hosts, attach to the surface of enterocytes and generate characteristic attaching and effacing (A/E) lesions. These lesions involve the collapse of host microvilli and the generation of pedestal‐like structures atop infected cells. Pedestal formation and disease progression is induced by bacterial proteins (effectors) that are translocated into the host cell cytoplasm by a syringe‐like type‐three secretion system (T3SS). The three major components of the host cell cytoskeleton; actin, microtubules and intermediate filaments, are all altered during EPEC pathogenesis. We have identified another major host cytoskeletal network that is involved in EPEC disease, the spectrin cytoskeleton. Here we demonstrate that spectrin is recruited to the base of EPEC pedestals and through the use of EPEC effector mutants, we show that this localization is mediated by the translocated intimin receptor (Tir). Spectrin knockdowns using siRNA have revealed that spectrin is necessary for pedestal formation to occur. Our findings provide the first evidence of spectrin's involvement in EPEC pathogenesis and identify it as a crucial protein involved in pedestal formation and disease progression.Grant Funding Source: CIHR, NSERC