A-EPEC (atypical enteropathogenic E. coli) is EPEC that have lost the EAF (EPEC adherence factor) plasmid. Some studies (Sousa & Dubreuil, 2001; Scotland et al., 1991) had shown that, probably, A-EPEC is another EPEC category associated with diarrhea of clinical importance. Recent attention has focused on greater understanding of atypical EPEC strains (Trabulsi et al., 2002). These strains more commonly cause diarrhea in industrialized nations than the typical EPEC strains.
In addition the atypical EPEC strains have animal and human reservoirs, whereas the typical isolates are almost always associated with human fecal contamination. The atypical isolates have the ability to cause A/E lesions but lack the EAF plasmids. They often have additional virulence factors not seen among the typical strains. For example, they have significant portions of the pO157 virulence plasmid common to enterohemorrhagic E. coli O157:H7 strains and may have a heat stable enterotoxin (EAST-1), (Ejidokun et al.,2006).
ENTEROHAEMORRAGIC E. coli(EHEC)
EHEC (enterohaemorragic E. coli) strains are implicated in food-borne diseases principally due to ingestion of uncooked mince meat and raw milk. These strains produce shigalike toxin 1 (stx1), shiga-like toxin 2 (stx2) and variants thereof. They are involved in episodes of diarrhea with complications.
Serotype O157:H7 is the prototype of increasing importance and is associated with hemorrhagic colitis, bloody diarrhea and the hemolytic uremic syndrome (HUS). EHEC typically cause an afebrile bloody colitis and, in about 10% of patients, this infection can be followed by HUS (Pickering et al., 1994). Like EPEC, EHEC elicit an attaching and effacing lesion of the intestinal mucosa, a phenotype that requires a functional eaeA chromosomal gene.
These organisms share the ability to cause A/E lesions with EPEC but enterohemorrhagic E. coli (EHEC) are set apart from EPEC by possession of Shiga-like toxins and the clinical presentation of their disease. EHEC cause disease of the large intestine that may present as simple watery diarrhea and then progress to bloody stools with ulcerations of the bowel. In a small subset of diseased individuals there is onset several days later of severe, lifethreatening hemolytic-uremic syndrome (HUS), (Feng et al.,2002).
HUS involves a triad of hemolytic anemia, thrombocytopenia and renal failure. The transmission of EHEC disease in humans is through ingestion of contaminated beef or foods contaminated with cattle feces.
In cattle, the EHEC strains are transient members of the intestinal microflora where they do not apparently cause disease. One of the remarkable features of EHEC is its low infection dose of 10–100 organisms. Clearly this microorganism has special acid-tolerance ability when compared to many other enteric bacterial pathogens.
Children under the age of five are the major victims of EHEC disease, although the elderly may also exhibit bloody diarrhea and HUS. Epidemiologically in the United States, Japan, and Great Britain, a single serotype O157:H7 is the most common EHEC strain. In other parts of the world, this strain can be observed causing disease, but other serotypes (e.g., O26 and O111) cause a similar disease as well. All factors that lead to HUS are unknown except Shiga toxin (sometimes
referred to as "Shiga-like toxin" or "verotoxin"), which probably plays an important role in renal injury. Purified Stx-1 injected intravenously in baboons leads to renal disease with histopathology similar to EHEC-mediated HUS (Tailor et al., 1999). The Shiga toxin inhibits protein synthesis through cleavage of ribosomal RNA. Because EHEC do not cause bacteremia, Shiga toxin is thought to be released while the organism is growing in the large bowel, where it gets disseminated systemically to cause damage to renal endothelial cells and release of inflammatory mediators that eventually damage the kidney. There are two evolutionarily related forms of Shiga toxin in E. coli (Shiga toxin 1 and Shiga toxin 2).
They share approximately 55% amino acid sequence similarity. Shiga toxin 1 is only different from the Shiga toxin of Shigella dysenteriae by a single amino acid substitution. There are many Shiga toxin positive E. coli strains (STEC) that are not associated with enterohemorrhagic colitis. It is a heterogeneous group that is occasionally associated with HUS, but their general benign nature may be due to their lack of the LEE pathogenicity island and plasmid virulence factors. The ubiquitous dissemination of the distribution of Shiga toxin genes among E. coli strains is due to their transmission as part of lambdoid phages.
The EHEC O157:H7 strain likely originated in an O55 EPEC strain where a series of genetic events lead to acquisition of shiga toxinencoding prophages and a large virulence plasmid, pO157. The precise role of pO157 in EHEC pathogenesis is unknown but may involve some putative toxin genes and a mucin-specific zincmetalloprotease, StcE (Grys et al., 2005).
ENTEROINVASIVE E. coli (EIEC)
EIEC (enteroinvasive E. coli) cause a broad spectrum of human’s diseases. They are biochemically, genetically and pathogenetically closely related to Shigella spp. Both characteristically cause an invasive inflammatory colitis, but either may also elicit a watery diarrhea syndrome indistinguishable from that caused by other E. coli pathogens. The pathogenesis of disease caused by EIEC and Shigella involves cellular invasion and spread, and requires specific chromosomal and plasmidborne virulence genes (Nataro & Kaper, 1998).
These organisms are pathogenetically so closely related to Shigella species that the nomenclature distinction is questionable. There are a few biochemical traits that can be used to distinguish enteroinvasive E. coli (EIEC) from Shigella, but the principal virulence genes are shared. The diagnostic confusion between Shigella and EIEC is evident in that EIEC isolates are nonmotile and 70% are nonlactose fermenters (Silva et al., 1980). In addition, EIEC share with Shigella the inability to decarboxylate lysine, a trait common to other E. coli. The traits that EIEC share with E. coli but not Shigella are the ability to produce gas fromglucose and fermentation of xylose.
EIEC cause invasive inflammatory colitis and dysentery with a clinical presentation (blood and mucous stools accompanied by fever and severe cramps) identical to the disease caused by Shigella species. EIEC/Shigella invade intestinal epithelium, principally in the large intestine. Once inside the cells, they lyse the phagocytic vesicle and replicate freely in the host cell cytoplasm.
The EIEC/Shigella cells then spread to neighboring host cells by a motility process whereby actin is nucleated on one pole of the bacillus and subsequent actin polymerization propels the bacterial cell (Goldberg & Theriot, 1995). Many of genes necessary for cellular invasion and disease are carried on a large (>200-kb) plasmid found in both EIEC and Shigella. A system of type III secretion genes important for delivery of modifiers of host cell signaling and membrane lysis are found on these plasmids (Ochei and Kolhatkar, 2000).
In addition, the plasmid encodes an outer membrane protein (IcsA) that is localized on one pole of the bacterium and directs the actin microfilament polymerization necessary for spread of bacteria to other host cells. EIEC/Shigella rarely invades the bloodstream, but they do invade the lamina propria immediately under the intestinal epithelium, where interaction with macrophages causes the release of pro-inflammatory mediators and even induction of apoptosis.
Interestingly, the inability to decarboxylate lysine, a trait shared by EIEC and Shigella, is the result of mutations and gene rearrangements at the cadC gene. The decarboxylation of lysine results in cadverine, which acts as an inhibitor of inflammation and migration of neutrophils into the lamina propria. The lack of this function is hypothesized to be a pathoadaptive trait that enables EIEC/Shigella to cause disease (Casalino et al., 2003).