The role of epithelial malfunction in the pathogenesis of enteropathogenic E. coli-induced diarrhea

Abstract

The homeostatic balance of the gastrointestinal tract relies on a single layer of epithelial cells, which assumes both digestive and protective functions. Enteric pathogens, including enteropathogenic Escherichia coli (EPEC), have evolved numerous mechanisms to disrupt basic intestinal epithelial functions, promoting the development of gastrointestinal disorders. Despite its non-invasive nature, EPEC inflicts severe damage to the intestinal mucosa, including the dysregulation of water and solute transport and the disruption of epithelial barrier structure and function. Despite the high prevalence and morbidity of disease caused by EPEC infections, the etiology of its pathogenesis remains incompletely understood. This review integrates the newest findings on EPEC-epithelial interactions with established mechanisms of disease in an attempt to give a comprehensive understanding of the cellular processes whereby this common pathogen may cause diarrheal illness.

Enterohaemorrhagic, but not enteropathogenic, Escherichia coli infection of epithelial cells disrupts signalling responses to tumour necrosis factor-alpha

“…It is of interest now to determine whether a similar pattern is found in the in vivo setting, by employing a relevant animal model of human disease. EPEC, which is related evolutionarily to EHEC O157 : H7, does not contain Shiga toxins but does possess the LEE pathogenicity island and produces attaching and effacing lesions on eukaryotic cells in tissue culture exposed to the human enteric pathogen (Lapointe et al, 2009). With respect to NF-kB signalling, previous studies have reported that EPEC inhibits IKK, MAPK and P-I3 kinase signal transduction pathways in a T3SS-dependent manner (Ruchaud-Sparagano et al, 2007).…”

Probiotic bacteria and intestinal epithelial barrier function

“…Interestingly, pathogens can alter barrier function by altering MLC phosphorylation. For example, both EPEC and H. pylori can activate MLCK, causing actomyosin ring contraction, disruption of TJ proteins, and increased permeability (36, 69,110,149,163). The regulation of Rho GTPases is tightly monitored in the cell, and either activation or inhibition of its ROCK phosphorylating capabilities can result in aberrant barrier function.…”

Enteric pathogens and gut function: Role of cytokines and STATs

“…These bacteria have evolved a number of strategies that allow them to directly augment, disrupt, or inhibit epithelial cell function including invasion of epithelial cells, molecular mimicry, activation of intracellular signaling pathways, formation of pores, and alteration of cytoskeleton-dependent functions. [33][34][35][36] There is a general consensus that A/E pathogens increase epithelial permeability 37 and induce changes in epithelial secretion and absorption that result in diarrhea. This topic was the focus of several recent excellent reviews.…”

“…This topic was the focus of several recent excellent reviews. 37,38 Although co-option of epithelial cell function to promote colonization is the initial action of A/E pathogens, the resulting upregulation of Th1 cytokines is important in sustaining initial bacterial effects on permeability. Of interest is that loss of absorptive surface is a consequence of infection, but the effects on epithelial permeability do not appear to be due to epithelial apoptosis.…”