ETEC: ETEC are the most common cause of diarrhea in children in developing countries and in travellers to these areas, and an important pathogen of weanling animals. Clinically, disease can range in severity from mild self-limiting to severe life-threatening cholera-like diarrhea. The pathogenesis of ETEC infection is largely explicable in terms of two important virulence attributes: the ability to adhere to epithelial cell surfaces and expression of entero-toxins.
Adhesion is mediated by ‘colonization factors’ (CFs), the nomenclature of which is very confusing. An attempt has been made to rationalize the situation for human ETECs by renaming them as coli surface antigens (CS, followed by a numeral, CS1, CS2 etc). E coli CFs are encoded on plasmids (which may also contain the genes for both types of enterotoxins described below), and determine both host and tissue specificity of infection. For example, important CFs produced by animal ETEC are not found on human strains, and CF K88 is found only in strains that infect pigs, whereas K99-expressing strains infect calves, lambs and pigs. CSs of human strains have been subdivided into four groups on a morphological basis — rigid rods, bundle forming, fibrillar and nonfibrillar — the structures of which have been schematized. Tissue tropism is best illustrated by the specificity of interaction exhibited by UPEC in which its ‘P’ fimbria interacts with the Gal(a1-4)gal oligosaccharide of the gycolipid part of blood group substance P expressed on uroepithelial cells.
Once ETECs have colonized, they produce enterotoxins, which can be of two types. Heat labile toxin (LT) is structurally and functionally homologous to CT and exists as two major antigenic groups (LT-I and LT-II), each of which has minor antigenic variants. In addition to LT, ETEC produces heat stable toxins (STs), which are nonantigenic, low molecular weight, cysteine-rich peptides that activate membrane-spanning guanylate cyclase, which causes the production of cGMP (a functional equivalent of cAMP), giving rise to a biochemical cascade resulting in the perturbation of ion transport systems as described above for CT. There are two unrelated classes of ST (STa [ST-I] and STb [ST-II]) encoded by plasmids (predominantly) and trans-posons. STa homologues are also produced by some strains of Yersinia enterocolitica and V cholerae non-O1. Another ST is produced by EAEC (enteroaggregative E coli heat-stable enterotoxin 1 [EAST1], see below) and it too may be produced by some strains of ETEC. ST-I enterotoxins may represent a class of long-lived superagonists of guanylin, a regulatory intestinal peptide.