The modulation of enteropathogenic E. coli infection by substrate stiffness

Enteropathogenic Escherichia coli (EPEC) is a Gram-negative foodborne bacterium that has been associated with many severe diarrhea outbreaks worldwide, especially in children under the age of five. EPEC is a pathogen that infects intestinal epithelial cells and causes several conditions ranging from asymptomatic colonization of the intestine to morbidity and even lethality. A hallmark of an EPEC infection is the formation of “attaching and effacing” histopathological lesions at the surface of enterocytes that are characterized by the destruction of the brush border microvilli and the formation of actin-rich pedestals beneath the bacterial attachment site. Like many Gram-negative bacteria, EPEC employs the Type III Secretion System (T3SS) to inject effector proteins essential for its infectivity, including its own receptor Tir, that lead to host cell cytoskeletal remodeling and promote the formation of these actin pedestals and intimate bacteria-host cell adherence. In addition to Tir, EPEC injects several other effector proteins that lead to various pathological phenotypes such as tight junction disruption, cell cycle arrest and apoptotic cell death. EPEC infection has been extensively studied using traditional tissue culture models; however, intestinal stiffness is more than 300,000 times softer than glass. Studying EPEC using polyacrylamide gels of physical compliance can provide a deeper understanding on its infection mechanism under mechanical conditions closer to its natural environment. Since substrate stiffness has known physiological effects on mammalian cytoskeletal organization and cell signaling, we hypothesize that tissue compliance will play an important role in the regulation of EPEC infection.M.S.Includes bibliographical reference