Although most E. coli are harmless commensals of the human and animal intestine, certain specific, highly-adapted E. coli strains are capable of causing a variety of different diseases. Infections due to pathogenic E. coli may be limited to colonization of a mucosal surface or can disseminate throughout the body and have been implicated in urinary tract infection, sepsis/meningitis and gastrointestinal infections (Nataro & Kaper, 1998). One of the most notable features of E. coli is broad diversity of disease-causing genotypes.
The diseases can encompass different symptoms and gastrointestinal tract 345 pathologies, but there are also diseases at extraintestinal sites. These different genotypes and their disease-causing abilities lead to categories of E. coli often referred to as pathotypes. There are seven intestinal and two extraintestinal pathotypes currently recognized. (Brüssow et al.,2004)
ENTEROTOXIGENIC E. coli (ETEC)
ETEC (enterotoxigenic E. coli) strains are a major cause of secretory diarrhea in both humans and animals. ETEC produce toxins which are heat-labile (LT)
and/or heat-stable (STa and STb) that are also causing diarrhea. A frequent cause of diarrhea in both humans and animals, enterotoxigenic E. coli (ETEC) are estimated to cause 600 million cases of human diarrhea and 800,000 deaths worldwide principally in children under the age of 5. Economically significant ETEC diarrheal disease in animals occurs in neonatal calves, pigs and lambs. ETEC cause watery diarrhea that can be mild in nature or in some instances can be a severe, cholera-like illness where rapid dehydration can be life-threatening. In endemic areas of ETEC-mediated diarrhea, infants and children under the age of 5 are the most commonly affected. ETEC exposure in endemic areas is one of the most common causes of traveler's diarrhea. One of the principal virulence factors for this pathogen is the heat-labile enterotoxin (LT), which interestingly shares structural and functional similarity to the Vibrio cholera cholera toxin. LT toxin has a classic AB toxin subunit holotoxin structure. The B subunits (as a pentamer) bind to host cell surface GM1 and GD1b gangliosides and the A subunit enzymatically ADP-ribosylates the α- subunit of stimulatory G protein. This G protein regulates host cell adenylate cyclase and LTmediated modification leads to its permanent activation and an increase in intracellular cAMP levels.
This eventually leads to activation of the chloride ion channel of the intoxicated cells, increased chloride ion secretion into the intestinal lumen, and decreased sodium and chloride absorption. The overall result is to reverse the normal intestinal osmotic gradient and cause a net water loss into the gut lumen. Aside from LT, many ETEC strains also express heat-stabile enterotoxins (STs), which also contribute to the watery diarrhea. There are two structurally distinct STs, STa and STb, (Chanishvili, 2012).
The STs are small polypeptides that share the common features of heat stability and multiple intramolecular disulfide bonds. The action of STa is well understood. It binds to the extracellular domain of plasma membraneembedded guanylate cyclase. The ETEC toxins are secreted in the terminal small intestine where the ETEC adhere by expression of a complex and diverse group of surface proteins commonly referred to as "colonization factors" (Gaastra and Svennerholm, 1996).
ENTEROPATHOGENIC E. coli (EPEC)
These organisms are a significant cause of infant diarrhea in developing nations. Enteropathogenic E. coli (EPEC) were historically recognized on the basis of serotypes such as O55:H6 and O127:H6. EPEC (enteropathogenic E. coli), an established etiological agent of human infantile diarrhea, is a pathogen that subverts intestinal epithelial cell function to produce distinctive “attaching and effacing” (A/E) lesions. These lesions are characterized by localized destruction (effacement) of brush border microvilli, intimate bacterial attachment to the host-cell membrane and formation of an actin-rich cytoskeletal structure beneath intimately attached bacteria.
In developing countries, enteropathogenic E. coli (EPEC) is one of the most common pathogens. In Brazil, for example, EPEC can be isolated from stools of over 40% of infants with acute diarrhea and was associated with a mortality of 7% (Fagundes Neto and Scaletsky, 2000). The pathogenesis of EPEC is in some way unique for enteric bacterial pathogens since it is essentially noninvasive and produces no toxins.
The attachment of EPEC to the epithelial cell, described as localized adherence, results in a socalled attaching and effacing lesion (A/E) (Celli et al., 2000). EPEC also uses its TTSS to deliver bacterial effector proteins like EspA and EspB into the host cell to alter the cytoskeleton (Knutton et al., 1998).
However, the most fascinating aspect of EPEC pathogenesis is that it inserts, through the type III secretion system, its own receptor into the host cell. Rather than searching for a receptor it provides its own receptor and uses it when needed.
Thus, EPEC is able to insert the Tir receptor into the host cell membrane where it serves as the receptor for the bacterial protein intimin after it is phosphorylated on tyrosine by the host cell (Deibel et al., 1998). EPEC disease is generally the result of growth of EPEC in the small intestine. EPEC cause a watery diarrhea that may contain mucus but typically does not have blood in it (Ochei and Kolhatkar, 2000).
Vomiting, fever, malaise and dehydration are also associated. The symptoms may last for a brief period of several days, although instances of long, chronic EPEC disease have been noted. Some of the mechanisms of EPEC pathogenesis are well understood. For example, the A/E lesion is the result of a complex system of EPEC proteins that are injected into the host intestinal epithelial cell, (Darnton et al.,2007).
The A/E lesion represents a dramatic rearrangement of the epithelial cytoskeleton where there is an accumulation of actin directly below the attached EPEC cell. This is described as an actin pedestal for the attached bacterial cell. There is a specific pathogenicity island, termed the"locus of enterocyte effacement" (LEE), that encodes the genes responsible for the A/E lesion.
The LEE encodes a type III secretion system that provides the intimate adhesion (intimin) its receptor (which is injected into and then presented on the surface of the host cell), and the injected proteins responsible for changes in host cell signaling mechanisms, including actin pedestal formation (Jerse, 1990).
Common to most EPEC strains are plasmids EAF ("EPEC adherence factor"), which encode an adherence factor, the bundle-forming pilus (bfp), (Nataro et al., 1987). Results of human volunteer studies indicate the EAF plasmid is necessary to cause disease (Levine et al., 1985). Although the A/E characteristic is critical for causing EPEC disease, probably through destruction of microvilli, the precise mechanism for the diarrhea is not completely understood and may reflect the diversity of EPEC strains.