EnterohemorrhagicEscherichia coliInduces Apoptosis Which Augments Bacterial Binding and Phosphatidylethanolamine Exposure on the Plasma Membrane Outer Leaflet

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a gastrointestinal pathogen that causes watery diarrhea and hemorrhagic colitis and can lead to serious and even fatal complications such as hemolytic uremic syndrome. We investigated the ability of EHEC to kill host cells using three human epithelial cell lines. Analysis of phosphatidylserine expression, internucleosomal cleavage of host cell DNA and morphological changes detected by electron microscopy changes revealed evidence of apoptotic cell death. The rates and extents of cell death were similar for both verotoxin-producing and nonproducing strains of EHEC as well as for a related gastrointestinal pathogen, enteropathogenic E. coli (EPEC). The induction of apoptosis by bacterial attachment was independent of verotoxin production and greater than that produced by a similar treatment with verotoxin alone. Expression of phosphatidylethanolamine, previously reported to bind EHEC and EPEC, was also increased on apoptotic cells but with little correlation to phosphatidylserine expression. Phosphatidylethanolamine levels but not phosphatidylserine levels on dying cells correlated with EHEC binding. Cells treated with phosphatidylethanolamine-containing liposomes also showed increased EHEC binding. These results suggest that bacterial induction of apoptosis offers an advantage for bacterial attachment by augmenting outer leaflet levels of the phosphatidylethanolamine receptor.

Shiga Toxin 1 Triggers a Ribotoxic Stress Response Leading to p38 and JNK Activation and Induction of Apoptosis in Intestinal Epithelial Cells

“…Studies from Barnett-Foster et al and Jones et al demonstrated that Shiga toxins may play a role in inducing apoptosis in some intestinal epithelial cell lines (3,17). Shiga toxins have previously been observed to mediate intestinal damage by cellular apoptosis in a rabbit ileal loop model (18).…”

Infection strategies of enteric pathogenic Escherichia coli

“…Like many enteric pathogens EPEC and EHEC are able to induce apoptosis upon infection. 180,181 However, apoptosis induction needs to be modulated in order to maintain an infective niche within a host, by balancing pro and anti-apoptotic effectors (Fig. 5E).…”

EspC Promotes Epithelial Cell Detachment by Enteropathogenic Escherichia coli via Sequential Cleavages of a Cytoskeletal Protein and then Focal Adhesion Proteins

“…Epithelial cell death is a well-known consequence of EPEC infection (32)(33)(34)(35)(36)(37). Furthermore, in human EPEC infection cases, pathological evidence of intestinal damage has been found (17,18,38).…”