E .coli that cause diarrhea are extremely common worldwide. These E. coli are classified by the characteristics of their virulence properties , and each group causes disease by a different mechanism—at least six of which have been characterized. The small or large bowel epithelial cell adherence properties are encoded by genes on plasmids. Similarly, the toxins often are plasmid or phage mediated.

Enteropathogenic E. coli (EPEC) are an important cause of diarrhea in infants, especially in developing countries. EPEC adhere to the mucosal cells of the small bowel. Pathogenicity requires two important factors, the bundle forming pilus encoded by a plasmid EPEC adherence factor (EAF) and the chromosomal locus of enterocyte effacement (LEE) pathogenicity island that promote the tight adherence characteristic of EPEC (attachment and effacement). After attachment, there is loss of microvilli (effacement); formation of filamentous actin pedestals or cuplike structures; and, occasionally, entry of the EPEC into the mucosal cells. Characteristic lesions can be seen on electron micrographs of small bowel biopsy lesions. The result of EPEC infection in infants is characterized by severe, watery diarrhea, vomiting, and fever, which are usually self-limited but can be prolonged or chronic. EPEC diarrhea has been associated with multiple specific serotypes of E coli; strains are identified by O antigen and occasionally by H antigen typing. A two-stage infection model using HEp-2 or HeLa cells also can be performed. Tests to identify EPEC are performed in reference laboratories. The duration of the EPEC diarrhea can be shortened and the chronic diarrhea cured by antibiotic treatment.

Enterotoxigenic E. coli (ETEC) are a common cause of “traveler’s diarrhea” and a very important cause of diarrhea in children less than 5 years of age in developing countries. ETEC colonization factors (pili known as colonization factor antigens [CFAs]) specific for humans promote adherence of ETEC to epithelial cells of the small bowel. Some strains of ETEC produce a heat-labile enterotoxin (LT) (molecular weight [MW], 80,000) that is under the genetic control of a plasmid and is closely related to cholera toxin. Its sub unit B attaches to the GM1 ganglioside in the apical mem brane of enterocytes and facilitates the entry of subunit A (MW, 26,000) into the cell, where the latter activates adenylyl cyclase. This markedly increases the local concentration of cyclic adenosine monophosphate (cAMP) after which ensues a complex cascade that involves the cystic fibrosis transmembrane conductance regulator. The end result is an intense and prolonged hypersecretion of water and chlorides and inhibition of the reabsorption of sodium. The gut lumen is distended with fluid, and hypermotility and diarrhea ensue, lasting for several days. LT is antigenic and cross-reacts with the enterotoxin of Vibrio cholerae, which has an identical mechanism of action. LT stimulates the production of neutralizing antibodies in the serum (and perhaps on the gut surface) of persons previously infected with enterotoxigenic E. coli. Persons residing in areas where such organisms are highly prevalent (eg, in some developing countries) are likely to possess antibodies and are less prone to develop diarrhea on reexposure to the LT-producing E coli. Assays for LT include (1) fluid accumulation in the intestines of laboratory animals, (2) typical cytologic changes in cultured Chinese hamster ovary cells or other cell lines, (3) stimulation of steroid production in cultured adrenal tumor cells, (4) binding and immunologic assays with standardized antisera to LT, and (5) detection of the genes that encode the toxins. These assays are done only in reference laboratories.

Some strains of ETEC produce the heat-stable enterotoxin ST_a (MW, 1500–4000), which is under the genetic control of a heterogeneous group of plasmids. ST_a activates guanylyl cyclase in enteric epithelial cells and stimulates fluid secretion. Many ST_a-positive strains also produce LT. The strains with both toxins produce a more severe diarrhea.

T he plasmids carrying the genes for enterotoxins (LT, ST) also may carry genes for the CFAs that facilitate the attachment of E coli strains to intestinal epithelium. Recognized colonization factors occur with particular frequency in some serotypes. Certain serotypes of ETEC occur worldwide; others have a limited recognized distribution. It is possible that virtually any E coli may acquire a plasmid encoding for enterotoxins. There is no definite association of ETEC with the EPEC strains causing diarrhea in children. Likewise, there is no association between enterotoxigenic strains and those able to invade intestinal epithelial cells.

Care in the selection and consumption of foods potentially contaminated with ETEC is highly recommended to help prevent traveler’s diarrhea. Antimicrobial prophylaxis can be effective but may result in increased antibiotic resistance in the bacteria and probably should not be uniformly recommended. When diarrhea develops, antibiotic treatment effectively shortens the duration of disease.

Shiga toxin-producing E. coli (STEC) are named for the cytotoxic toxins they produce. There are at least two antigenic forms of the toxin referred to as Shiga-like toxin 1 and Shiga like toxin 2. STEC has been associated with mild non-bloody diarrhea, hemorrhagic colitis, a severe form of diarrhea, and with hemolytic uremic syndrome, a disease resulting in acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Shiga-like toxin 1 is identical to the Shiga toxin of Shigella dysenteriae type 1, and Shiga-like toxin 2 also has many properties that are similar to the Shiga toxin; how ever, the two toxins are antigenically and genetically distinct. A low infectious dose (< 200 CFU) is associated with infection. Of the more than 150 E. coli serotypes that produce Shiga toxin, O157:H7 is the most common and is the one that can be identified most readily in clinical specimens. STEC O157:H7 does not use sorbitol, unlike most other E coli, and is negative (clear colonies) on sorbitol MacConkey agar (sorbitol is used instead of lactose); O157:H7 strains also are negative on MUG tests . Many of the non-O157 serotypes may be sorbitol positive when grown in culture. Specific anti sera are used to identify the O157:H7 strains. Tests for the detection of both Shiga toxins using commercially available enzyme immunoassays (EIAs) are done in many laboratories. Other sensitive test methods include cell culture cytotoxin testing using Vero cells and polymerase chain reaction for the direct detection of toxin genes directly from stool samples. Many cases of hemorrhagic colitis and its associated complications can be prevented by thoroughly cooking ground beef and by avoiding unpasteurized products such as apple cider. In 2011, the largest outbreak of hemorrhagic colitis attributed to a non-O157 serotype—namely, E coli O104:H4—was related to consumption of contaminated sprouts in Germany. This organism had increased virulence characterized by enhanced adherence as well as the production of Shiga-like toxins (see reference by Buchholz et al, 2011).

Enteroinvasive E. coli (EIEC) produce a disease very similar to shigellosis. The disease occurs most commonly in children in developing countries and in travelers to these countries. Similar to Shigella, EIEC strains are nonlactose or late lactose fermenters and are nonmotile. EIEC produce dis ease by invading intestinal mucosal epithelial cells.

Enteroaggregative E .coli (EAEC) causes acute and chronic diarrhea (>14 days in duration) in persons in developing countries. These organisms also are the cause of foodborne illnesses in industrialized countries and have been associated with traveler’s diarrhea and persistent diarrhea in patients with HIV. They are characterized by their specific patterns of adherence to human cells. This group of diarrheagenic E. coli is quite heterogeneous, and the exact pathogenic mechanisms are still not completely elucidated. Some strains of EAEC produce ST like toxin , others a plasmid-encoded enterotoxin that produces cellular dam age; and still others, a hemolysin. Diagnosis can be suspected clinically but requires confirmation by tissue culture adhesion assays not readily availa