Cross-Reactive Protection against Enterohemorrhagic Escherichia coli Infection by Enteropathogenic E. coli in a Mouse Model

Abstract

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are related attaching and effacing (A/E) pathogens. The genes responsible for the A/E pathology are carried on a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Both pathogens share a high degree of homology in the LEE and additional O islands. EHEC prevalence is much lower in areas where EPEC is endemic. This may be due to the development of antibodies against common EPEC and EHEC antigens. This study investigated the hypothesis that EPEC infections may protect against EHEC infections. We used a mouse model to inoculate BALB/c mice intragastrically, first with EPEC and then with EHEC (E. coli O157:H7). Four control groups received either a nonpathogenic E. coli (NPEC) strain followed by EHEC (NPEC/EHEC), phosphate-buffered saline (PBS) followed by EHEC (PBS/EHEC), EPEC/PBS, or PBS/PBS. Mice were monitored for weight loss and symptoms. EPEC colonized the intestine after challenge, and mice developed serum antibodies to intimin and E. coli secreted protein B (encoded in the LEE). Prechallenge with an EPEC strain had a protective effect after EHEC infection, as only a few mice developed mild symptoms, from which they recovered. These mice had an increase in body weight similar to that in control animals, and tissue morphology exhibited mild intestinal changes and normal renal histology. All mice that were not prechallenged with the EPEC strain developed mild to severe symptoms after EHEC infection, with weight loss as well as intestinal and renal histopathological changes. These data suggest that EPEC may protect against EHEC infection in this mouse model.Enterohemorrhagic Escherichia coli (EHEC) is a causative agent of diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS) (17). EHEC is characterized by the presence of Shiga toxin (Stx) as a major virulence factor (26). Enteropathogenic Escherichia coli (EPEC) is a leading cause of acute diarrhea among infants living under poor social conditions in developing countries (35). Typical EPEC is characterized by the presence of a virulence plasmid know as the EAF (EPEC adherence factor) (49). The EAF plasmid contains a cluster of genes encoding the bundle-forming pili (Bfp), required for localized adherence to epithelial cells (15). In contrast to EHEC, EPEC strains do not produce Stx.Both pathogens induce characteristic attaching and effacing (A/E) lesions on intestinal enterocytes, characterized by intimate bacterial adhesion, destruction of microvilli, and accumulation of polymerized actin in pedestals beneath intimately attached bacteria (24). Bacterial factors required for the formation of the A/E lesion are encoded on a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE) (12), which contains eae, encoding the adhesin intimin (22); esc and sep, encoding a type III secretion apparatus (12); and genes encoding proteins that are secreted via the type III secretion system, including E. coli secreted protein A (EspA),...

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

“…In fact, intragastric immunization with a clinical isolate EPEC O126:H6 and challenge using the EHEC O157:H7 wild-type strain yielded sick mice, but with no dead mice reported. Interestingly, it was also shown that the EspB and intimin antibodies produced after the EPEC vaccination were cross-reactive against EspB (translocated protein and effector that prevents phagocytosis) and intimin from EHEC (Calderon Toledo et al, 2011 ).…”

Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection

“…Although mice do not developed the symptoms associated with diarrheal disease observed in humans, development of murine models of E. coli O157:H7 infection, including axenic (no indigenous intestinal flora) or streptomycin-treated Balb/c (reduced normal flora) mice have proved to be useful for EHEC colonization and candidate vaccine testing [20]. Because the lack of a naturally EHEC infected mouse model is a major obstacle, the ability of Citrobacter rodentium to naturally colonize and form A/E lesions in mice has been explored as a alternative for A/E pathogens-mediated disease and could be used for vaccine evaluation [54]. As such, a new Stx-expressing C. rodentium strain has been developed to resemble EHEC infection in mice [55].…”

Four types of Bifidobacteria trigger autophagy response in intestinal epithelial cells

“…EPEC, characterized by their pathogenic phenotype and subsequent inflammatory response, is a chief etiology of diarrhea and intestinal inflammation in human beings. EPEC infection in cultured IEC has been shown to induce attaching‐and‐effacing (A/E) lesions . To our knowledge, the regulation of EPEC on autophagy in IEC has not been reported yet.…”