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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI016776-13
Application #
3566939
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1979-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Qu, Z H; Finkelstein, R A (1993) Checkerboard immunoblotting recognizes twenty epitopes among the B subunit proteins of the cholera enterotoxin family. Electrophoresis 14:899-901
Finkelstein, R A; Boesman-Finkelstein, M; Chang, Y et al. (1992) Vibrio cholerae hemagglutinin/protease, colonial variation, virulence, and detachment. Infect Immun 60:472-8
Kazemi, M; Finkelstein, R A (1991) Mapping epitopic regions of cholera toxin B-subunit protein. Mol Immunol 28:865-76
Qu, Z H; Boesman-Finkelstein, M; Kazemi, M et al. (1991) Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. J Infect Dis 164:796-9
Qu, Z H; Boesman-Finkelstein, M; Finkelstein, R A (1991) Urea-induced release of heat-labile enterotoxin from Escherichia coli. J Clin Microbiol 29:773-7
Boesman-Finkelstein, M; Finkelstein, R A (1991) Bovine lactogenic immunity against pediatric enteropathogens. Adv Exp Med Biol 310:361-7
Kazemi, M; Finkelstein, R A (1991) Identification of epitopes of the receptor binding subunit of cholera toxin by synthetic peptide and CBIB approaches. Adv Exp Med Biol 303:249-54
Hase, C C; Finkelstein, R A (1991) Cloning and nucleotide sequence of the Vibrio cholerae hemagglutinin/protease (HA/protease) gene and construction of an HA/protease-negative strain. J Bacteriol 173:3311-7
Hase, C C; Finkelstein, R A (1990) Comparison of the Vibrio cholerae hemagglutinin/protease and the Pseudomonas aeruginosa elastase. Infect Immun 58:4011-5
Brickman, T J; Boesman-Finkelstein, M; Finkelstein, R A et al. (1990) Molecular cloning and nucleotide sequence analysis of cholera toxin genes of the CtxA- Vibrio cholerae strain Texas Star-SR. Infect Immun 58:4142-4

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