It is now evident that there is a family of diarrheagenic enterotoxins which are structurally, functionally and immunologically related to the prototype, the cholera entertoxin (a.k.a. choleragen, cholera toxin, or CT), which was first isolated to homogeneity in 1969. The family is known to include several variations of CT; heat-labile enterotoxins (a.k.a. LTs) from diarrheagenic strains of Escherichia coli of human (H) origin; LT from strains of E. coli of porcine (P) origin; a distinct LT, LT-II, from an E. coli strain of bovine origin; and cholera/coli related enterotoxins from Salmonellae, Aeromonas hydrophila, Campylobacter jejuni, Vibrio cholerae non-01, and V. mimicus. For others, the evidence is thus far only circumstantial. Enterotoxigenic E. coli have been estimated to cause as many as 650 million cases of diarrhea and 800,000 deaths in children per year in Asia, Africa, and Latin America. The incidence and impact of other enterotoxigenic bacteria is unknown nor are effective control measures - vaccines - available. The toxins and their antibodies which have studied differ in quantitative cross- neutralization. The goal of this continuing research is to contribute further to the basic understanding of this important family of toxins by: a) developments of rapid, reliable, and economical methods for the detection of enterotoxinogenic bacteria and their toxins in clinical specimens; b) isolation and characterization of additional members; c) the definition of common and toxin-unique antigenic sites (epitopes) on the immunodominant B (binding) subunit proteins. The technology to be used: involves; a) immunologic assays (enzyme-linked immunosorption assays (ELISA), latex particle agglutination tests (LPAT), immuno-blotting precipitin and neutralization tests) using polyclonal and monoclonal antibodies; b) production, isolation, purification and characterization of new toxins and components peptides by conventional, immuno-affinity and high performance liquid chromatography (HPLC) methods; and c) the application of genetic probes and synthetic oligonucleotides for detection and cloning of toxin genes both for diagnosis and characterization of the gene products.
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