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Structure, Enterotoxicity, and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Stable Type I Toxin (STa) and Derivatives

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Microbial Toxins

Part of the book series: Toxinology ((TOXI))

Abstract

Heat-stable toxin type I (STa) is one of the two major types of enterotoxins produced by enterotoxigenic Escherichia coli (ETEC) bacteria that cause children’s diarrhea and travelers’ diarrhea. STa toxicity and its antigenicity, when coupled to a carrier protein, are associated with unique protein structural characteristics. Changes of primary structure of STa molecule result in reduction or loss of enterotoxicity and alteration of host receptor binding activity as well as immunogenicity potency. This chapter will briefly review structure, enterotoxicity, and immunogenicity potency of STa toxin and derived STa mutants.

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References

  • Aimoto S, Takao T, Shimonishi Y, Hara S, Takeda T, Takeda Y, et al. Amino-acid sequence of a heat-stable enterotoxin produced by human enterotoxigenic Escherichia coli. Eur J Biochem/FEBS. 1982;129(2):257–63. PubMed PMID: 6759126.

    Article  CAS  Google Scholar 

  • Aimoto S, Watanabe H, Ikemura H, Shimonishi Y, Takeda T, Takeda Y, et al. Chemical synthesis of a highly potent and heat-stable analog of an entero-toxin produced by a human strain of entero-toxigenic Escherichia coli. Biochem Biophys Res Commun. 1983;112(1):320–6. doi:10.1016/0006-291x(83)91833-8. PubMed PMID: WOS:A1983QL88700046.

    Article  CAS  PubMed  Google Scholar 

  • Albano F, Thompson MR, Orru S, Scaloni A, Musetta A, Pucci P, et al. Structural and functional features of modified heat-stable toxins produced by enteropathogenic Klebsiella cells. Pediatr Res. 2000;48(5):685–90. doi:10.1203/00006450-200011000-00022. PubMed PMID: 11044492.

    Article  CAS  PubMed  Google Scholar 

  • Alderete JF, Robertson DC. Purification and chemical characterization of the heat-stable enterotoxin produced by porcine strains of enterotoxigenic Escherichia coli. Infect Immun. 1978;19(3):1021–30. PubMed PMID: 346481; PubMed Central PMCID: PMCPMC422292.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aref NE, Saeed AM. Generation of high-titer of neutralizing polyclonal antibodies against heat-stable enterotoxin (STa) of enterotoxigenic Escherichia coli. Vaccine. 2012;30(45):6341–6. doi:10.1016/j.vaccine.2012.06.064. PubMed PMID: 22766246; PubMed Central PMCID: PMCPMC3455136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arita M, Takeda T, Honda T, Miwatani T. Purification and characterization of Vibrio cholerae non-O1 heat-stable enterotoxin. Infect Immun. 1986;52(1):45–9. PubMed PMID: 3957432; PubMed Central PMCID: PMCPMC262195.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Arita M, Honda T, Miwatani T, Takeda T, Takao T, Shimonishi Y. Purification and characterization of a heat-stable enterotoxin of Vibrio mimicus. FEMS Microbiol Lett. 1991;63(1):105–10. PubMed PMID: 2044934.

    Article  CAS  PubMed  Google Scholar 

  • Back E, Mollby R, Kaijser B, Stintzing G, Wadstrom T, Habte D. Enterotoxigenic Escherichia coli and other gram-negative bacteria of infantile diarrhea: surface antigens, hemagglutinins, colonization factor antigen, and loss of enterotoxigenicity. J Infect Dis. 1980;142(3):318–27. PubMed PMID: 7003030.

    Article  CAS  PubMed  Google Scholar 

  • Basu N, Arshad N, Visweswariah SS. Receptor guanylyl cyclase C (GC-C): regulation and signal transduction. Mol Cell Biochem. 2010;334(1–2):67–80. doi:10.1007/s11010-009-0324-x. PubMed PMID: 19960363.

    Article  CAS  PubMed  Google Scholar 

  • Batisson I, Der Vartanian M. Contribution of defined amino acid residues to the immunogenicity of recombinant Escherichia coli heat-stable enterotoxin fusion proteins. FEMS Microbiol Lett. 2000;192(2):223–9. PubMed PMID: 11064199.

    Article  CAS  PubMed  Google Scholar 

  • Batisson I, Der Vartanian M, Gaillard-Martinie B, Contrepois M. Full capacity of recombinant Escherichia coli heat-stable enterotoxin fusion proteins for extracellular secretion, antigenicity, disulfide bond formation, and activity. Infect Immun. 2000;68(7):4064–74. Epub 2000/06/17. PubMed PMID: 10858223; PubMed Central PMCID: PMC101696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Black RE. Epidemiology of travelers’ diarrhea and relative importance of various pathogens. Rev Infect Dis. 1990;12 Suppl 1:S73–9. Epub 1990/01/01. PubMed PMID: 2406860.

    Article  PubMed  Google Scholar 

  • Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375(9730):1969–87. PubMed PMID: 20466419.

    Article  PubMed  Google Scholar 

  • Brandwein H, Deutsch A, Thompson M, Giannella R. Production of neutralizing monoclonal antibodies to Escherichia coli heat-stable enterotoxin. Infect Immun. 1985;47(1):242–6. PubMed PMID: 3880723; PubMed Central PMCID: PMCPMC261502.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burgess MN, Bywater RJ, Cowley CM, Mullan NA, Newsome PM. Biological evaluation of a methanol-soluble, heat-stable Escherichia coli enterotoxin in infant mice, pigs, rabbits, and calves. Infect Immun. 1978;21(2):526–31. PubMed PMID: 357288; PubMed Central PMCID: PMCPMC422027.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Burke V, Gracey M, Robinson J, Peck D, Beaman J, Bundell C. The microbiology of childhood gastroenteritis: Aeromonas species and other infective agents. J Infect Dis. 1983;148(1):68–74. PubMed PMID: 6886488.

    Article  CAS  PubMed  Google Scholar 

  • Cardenas L, Clements JD. Development of mucosal protection against the heat-stable enterotoxin (ST) of Escherichia coli by oral immunization with a genetic fusion delivered by a bacterial vector. Infect Immun. 1993;61(11):4629–36. PubMed PMID: 8406860; PubMed Central PMCID: PMCPMC281214.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carpick BW, Gariepy J. Structural characterization of functionally important regions of the Escherichia coli heat-stable enterotoxin STIb. Biochemistry. 1991;30(19):4803–9. PubMed PMID: 2029521.

    Article  CAS  PubMed  Google Scholar 

  • Carrithers SL, Ott CE, Hill MJ, Johnson BR, Cai W, Chang JJ, et al. Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C receptor. Kidney Int. 2004;65(1):40–53. doi:10.1111/j.1523-1755.2004.00375.x. PubMed PMID: 14675035.

    Article  CAS  PubMed  Google Scholar 

  • Chao AC, de Sauvage FJ, Dong YJ, Wagner JA, Goeddel DV, Gardner P. Activation of intestinal CFTR Cl- channel by heat-stable enterotoxin and guanylin via cAMP-dependent protein kinase. EMBO J. 1994;13(5):1065–72. PubMed PMID: 7510634; PubMed Central PMCID: PMCPMC394914.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Choudhry MA, Gupta S, Yadava JN. Guinea-pig ileal loop assay: a better replacement of the suckling mouse assay for detection of heat-stable enterotoxins of Escherichia coli. J Trop Med Hyg. 1991;94(4):234–40. PubMed PMID: 1880824.

    CAS  PubMed  Google Scholar 

  • Clements JD. Construction of a nontoxic fusion peptide for immunization against Escherichia coli strains that produce heat-labile and heat-stable enterotoxins. Infect Immun. 1990;58(5):1159–66. PubMed PMID: 2182535; PubMed Central PMCID: PMCPMC258604.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crane JK, Wehner MS, Bolen EJ, Sando JJ, Linden J, Guerrant RL, et al. Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of Escherichia coli (STa) and protein kinase C. Infect Immun. 1992;60(12):5004–12. Epub 1992/12/01. PubMed PMID: 1360449; PubMed Central PMCID: PMC258269.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB. Recent advances in understanding enteric pathogenic Escherichia coli. Clin Microbiol Rev. 2013;26(4):822–80. doi:10.1128/CMR.00022-13. PubMed PMID: 24092857; PubMed Central PMCID: PMCPMC3811233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuthbert AW, Hickman ME, MacVinish LJ, Evans MJ, Colledge WH, Ratcliff R, et al. Chloride secretion in response to guanylin in colonic epithelial from normal and transgenic cystic fibrosis mice. Br J Pharmacol. 1994;112(1):31–6. PubMed PMID: 7518307; PubMed Central PMCID: PMCPMC1910279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Sauvage FJ, Camerato TR, Goeddel DV. Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin. J Biol Chem. 1991;266(27):17912–8. PubMed PMID: 1680854.

    PubMed  Google Scholar 

  • Dean AG, Ching YC, Williams RG, Harden LB. Test for Escherichia coli enterotoxin using infant mice: application in a study of diarrhea in children in Honolulu. J Infect Dis. 1972;125(4):407–11. PubMed PMID: 4553083.

    Article  CAS  PubMed  Google Scholar 

  • Delor I, Kaeckenbeeck A, Wauters G, Cornelis GR. Nucleotide sequence of yst, the Yersinia enterocolitica gene encoding the heat-stable enterotoxin, and prevalence of the gene among pathogenic and nonpathogenic yersiniae. Infect Immun. 1990;58(9):2983–8. PubMed PMID: 2201642; PubMed Central PMCID: PMCPMC313599.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Deng G, Li W, Wu X, Bao S, Zeng J, Zhao N, et al. Immunogenicity and protective efficacy of a recombinant adenoviral based vaccine expressing heat-stable enterotoxin (STa) and K99 adhesion antigen of enterotoxigenic Escherichia coli in mice. Mol Immunol. 2015;68(2 Pt C):684–91. doi:10.1016/j.molimm.2015.10.016. PubMed PMID: 26589454.

    Article  CAS  PubMed  Google Scholar 

  • Dobrescu L, Huygelen C. Susceptibility of the mouse intestine to heat-stable enterotoxin produced by enteropathogenic Escherichia coli of porcine origin. Appl Microbiol. 1973;26(3):450–1. PubMed PMID: 4584587; PubMed Central PMCID: PMCPMC379818.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eaglestone S, Hirst TR. Preparation of a fusion protein for vaccination against Escherichia coli enterotoxins. Biochem Soc Trans. 1995;23(1):54S. PubMed PMID: 7758770.

    Article  CAS  PubMed  Google Scholar 

  • Evans DG, Evans Jr DJ, Pierce NF. Differences in the response of rabbit small intestine to heat-labile and heat-stable enterotoxins of Escherichia coli. Infect Immun. 1973;7(6):873–80. PubMed PMID: 4577415; PubMed Central PMCID: PMCPMC422777.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Field M, Graf Jr LH, Laird WJ, Smith PL. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A. 1978;75(6):2800–4. PubMed PMID: 26915; PubMed Central PMCID: PMCPMC392652.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forte LR, Eber SL, Turner JT, Freeman RH, Fok KF, Currie MG. Guanylin stimulation of Cl- secretion in human intestinal T84 cells via cyclic guanosine monophosphate. J Clin Invest. 1993;91(6):2423–8. doi:10.1172/JCI116476. PubMed PMID: 8390480; PubMed Central PMCID: PMCPMC443301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frantz JC, Robertson DC. Immunological properties of Escherichia coli heat-stable enterotoxins: development of a radioimmunoassay specific for heat-stable enterotoxins with suckling mouse activity. Infect Immun. 1981;33(1):193–8. PubMed PMID: 6167519; PubMed Central PMCID: PMCPMC350677.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frantz JC, Bhatnagar PK, Brown AL, Garrett LK, Hughes JL. Investigation of synthetic Escherichia coli heat-stable enterotoxin as an immunogen for swine and cattle. Infect Immun. 1987;55(5):1077–84. PubMed PMID: 3552985; PubMed Central PMCID: PMCPMC260471.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gariepy J, Schoolnik GK. Design of a photoreactive analogue of the Escherichia coli heat-stable enterotoxin STIb: use in identifying its receptor on rat brush border membranes. Proc Natl Acad Sci U S A. 1986;83(2):483–7. PubMed PMID: 3510436; PubMed Central PMCID: PMCPMC322884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gariepy J, Lane A, Frayman F, Wilbur D, Robien W, Schoolnik GK, et al. Structure of the toxic domain of the Escherichia coli heat-stable enterotoxin ST I. Biochemistry. 1986;25(24):7854–66. PubMed PMID: 3801445.

    Article  CAS  PubMed  Google Scholar 

  • Gariepy J, Judd AK, Schoolnik GK. Importance of disulfide bridges in the structure and activity of Escherichia coli enterotoxin ST1b. Proc Natl Acad Sci U S A. 1987;84(24):8907–11. PubMed PMID: 2827159; PubMed Central PMCID: PMCPMC299660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germani Y, deRocquigny H, Guesdon JL. Escherichia coli heat-stable enterotoxin (STa)-biotin conjugates for the titration of STa antisera by an enzyme-linked immunosorbent assay. J Immunol Methods. 1992;146(1):25–32. PubMed PMID: 1735779.

    Article  CAS  PubMed  Google Scholar 

  • Germani Y, De Roquigny H, Begaud E. Escherichia coli heat-stable enterotoxin (STa)-biotin enzyme-linked immunosorbent assay (STa-biotin ELISA). J Immunol Methods. 1994;173(1):1–5. PubMed PMID: 8034976.

    Article  CAS  PubMed  Google Scholar 

  • Giannella RA. Suckling mouse model for detection of heat-stable Escherichia coli enterotoxin: characteristics of the model. Infect Immun. 1976;14(1):95–9. PubMed PMID: 780280; PubMed Central PMCID: PMCPMC420849.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Giannella RA, Drake KW, Luttrell M. Development of a radioimmunoassay for Escherichia coli heat-stable enterotoxin: comparison with the suckling mouse bioassay. Infect Immun. 1981;33(1):186–92. PubMed PMID: 7021423; PubMed Central PMCID: PMC350676.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Giannella RA, Luttrell M, Thompson M. Binding of Escherichia coli heat-stable enterotoxin to receptors on rat intestinal cells. Am J Physiol. 1983;245(4):G492–8. PubMed PMID: 6312810.

    CAS  PubMed  Google Scholar 

  • Guarino A, Capano G, Malamisura B, Alessio M, Guandalini S, Rubino A. Production of Escherichia coli STa-like heat-stable enterotoxin by Citrobacter freundii isolated from humans. J Clin Microbiol. 1987a;25(1):110–4. PubMed PMID: 3539984; PubMed Central PMCID: PMCPMC265835.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guarino A, Cohen M, Thompson M, Dharmsathaphorn K, Giannella R. T84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin. Am J Physiol. 1987b;253(6 Pt 1):G775–80. PubMed PMID: 2892417.

    CAS  PubMed  Google Scholar 

  • Guarino A, Giannella R, Thompson MR. Citrobacter freundii produces an 18-amino-acid heat-stable enterotoxin identical to the 18-amino-acid Escherichia coli heat-stable enterotoxin (ST Ia). Infect Immun. 1989;57(2):649–52. PubMed PMID: 2912902; PubMed Central PMCID: PMCPMC313149.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guerrant RL, Hughes JM, Chang B, Robertson DC, Murad F. Activation of intestinal guanylate cyclase by heat-stable enterotoxin of Escherichia coli: studies of tissue specificity, potential receptors, and intermediates. J Infect Dis. 1980;142(2):220–8. Epub 1980/08/01. PubMed PMID: 6106030.

    Article  CAS  PubMed  Google Scholar 

  • Guerrant RL, Kosek M, Moore S, Lorntz B, Brantley R, Lima AA. Magnitude and impact of diarrheal diseases. Arch Med Res. 2002;33(4):351–5. PubMed PMID: 12234524.

    Article  PubMed  Google Scholar 

  • Guzman-Verduzco LM, Kupersztoch YM. Fusion of Escherichia coli heat-stable enterotoxin and heat-labile enterotoxin B subunit. J Bacteriol. 1987;169(11):5201–8. PubMed PMID: 3312169; PubMed Central PMCID: PMCPMC213927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gyles CL. Escherichia coli enterotoxins. In: Gyles CL, editor. Escherichia coli in domestic animals and humans. Oxon: CAB International; 1994. p. 337–64.

    Google Scholar 

  • Hakki S, Robertson DC, Waldman SA. A 56 kDa binding protein for Escherichia coli heat-stable enterotoxin isolated from the cytoskeleton of rat intestinal membrane does not possess guanylate cyclase activity. Biochim Biophys Acta. 1993;1152(1):1–8. PubMed PMID: 8104484.

    Article  CAS  PubMed  Google Scholar 

  • Hill DR, Beeching N. Travelers’ diarrhea. Curr Opin Infect Dis. 2010;23(5):481–7.

    Article  PubMed  Google Scholar 

  • Hirayama T. Heat-stable enterotoxin of Escherichia coli. In: Moss J, Iglewski B, Vaughan M, Tu AT, editors. Bacterial toxins and virulence factors in disease. New York: Marcel Dekker; 1995. p. 281–96.

    Google Scholar 

  • Hughes JM, Murad F, Chang B, Guerrant RL. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature. 1978;271(5647):755–6. PubMed PMID: 203862.

    Article  CAS  PubMed  Google Scholar 

  • Hugues M, Crane M, Hakki S, O’Hanley P, Waldman SA. Identification and characterization of a new family of high-affinity receptors for Escherichia coli heat-stable enterotoxin in rat intestinal membranes. Biochemistry. 1991;30(44):10738–45. PubMed PMID: 1681902.

    Article  CAS  PubMed  Google Scholar 

  • Ikemura H, Yoshimura S, Aimoto S, Shimonishi Y, Hara S, Takeda T, et al. Synthesis of a heat-stable entero-toxin (Sth) produced by a human strain Sk-1 of entero-toxigenic Escherichia coli. Bull Chem Soc Jpn. 1984;57(9):2543–9. doi:10.1246/bcsj.57.2543. PubMed PMID: WOS:A1984TK78300037.

    Article  CAS  Google Scholar 

  • Jacks TM, Wu BJ. Biochemical properties of Escherichia coli low-molecular-weight, heat-stable enterotoxin. Infect Immun. 1974;9(2):342–7. PubMed PMID: 4593342; PubMed Central PMCID: PMCPMC414807.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF. Partial purification and properties of Enterobacter cloacae heat-stable enterotoxin. Infect Immun. 1976;13(5):1307–14. PubMed PMID: 5376; PubMed Central PMCID: PMCPMC420757.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Clements JD. Development of a vaccine of cross-linked heat-stable and heat-labile enterotoxins that protects against Escherichia coli producing either enterotoxin. Infect Immun. 1982;37(2):550–7. PubMed PMID: 6749682; PubMed Central PMCID: PMCPMC347569.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Houghten RA. Protection in rabbits immunized with a vaccine of Escherichia coli heat-stable toxin cross-linked to the heat-labile toxin B subunit. Infect Immun. 1983a;40(3):888–93. PubMed PMID: 6682834; PubMed Central PMCID: PMCPMC348135.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Clements JD, Houghten RA. Protection against human and porcine enterotoxigenic strains of Escherichia coli in rats immunized with a cross-linked toxoid vaccine. Infect Immun. 1983b;40(3):924–9. PubMed PMID: 6343245; PubMed Central PMCID: PMCPMC348140.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Houghten RA. Properties of cross-linked toxoid vaccines made with hyperantigenic forms of synthetic Escherichia coli heat-stable toxin. Infect Immun. 1984;44(2):268–73. PubMed PMID: 6425218; PubMed Central PMCID: PMCPMC263512.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Houghten RA. Mucosal antitoxin response in volunteers to immunization with a synthetic peptide of Escherichia coli heat-stable enterotoxin. Infect Immun. 1985;50(1):328–32. PubMed PMID: 3899936; PubMed Central PMCID: PMCPMC262178.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klipstein FA, Engert RF, Houghten RA. Immunisation of volunteers with a synthetic peptide vaccine for enterotoxigenic Escherichia coli. Lancet. 1986;1(8479):471–2. PubMed PMID: 2869210.

    Article  CAS  PubMed  Google Scholar 

  • Kopic S, Saleh A, and Geilbel JP. The heat-stable and heat-labile enterotoxins produced by enterotoxigenic Escherichia coli. In: Morabito S, editor. Pathogenic Escherichia coli – molecular and cellular microbiology. Norfolk: Caister Academic Press; 2014. p. 139–60.

    Google Scholar 

  • Kopic S, Murek M, Geibel JP. Commentary on ‘Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof’. Exp Physiol. 2010;95(4):484–5. doi:10.1113/expphysiol.2009.051912. PubMed PMID: 20233894.

    Article  PubMed  Google Scholar 

  • Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, et al. The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study. Clin Infect Dis. 2012;55 Suppl 4:S232–45. doi:10.1093/cid/cis753. PubMed PMID: 23169936; PubMed Central PMCID: PMC3502307.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case–control study. Lancet. 2013;382(9888):209–22. doi:10.1016/S0140-6736(13)60844-2. PubMed PMID: 23680352.

    Article  PubMed  Google Scholar 

  • Krause WJ, Cullingford GL, Freeman RH, Eber SL, Richardson KC, Fok KF, et al. Distribution of heat-stable enterotoxin/guanylin receptors in the intestinal tract of man and other mammals. J Anat. 1994;184(Pt 2):407–17. PubMed PMID: 8014132; PubMed Central PMCID: PMCPMC1260001.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kubota H, Hidaka Y, Ozaki H, Ito H, Hirayama T, Takeda Y, et al. A long-acting heat-stable enterotoxin analog of enterotoxigenic Escherichia coli with a single d-amino acid. Biochem Biophys Res Commun. 1989;161(1):229–35. PubMed PMID: 2543409.

    Article  CAS  PubMed  Google Scholar 

  • Kuhn M, Adermann K, Jahne J, Forssmann WG, Rechkemmer G. Segmental differences in the effects of guanylin and Escherichia coli heat-stable enterotoxin on Cl- secretion in human gut. J Physiol. 1994;479(Pt 3):433–40. PubMed PMID: 7837099; PubMed Central PMCID: PMCPMC1155761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuno T, Kamisaki Y, Waldman SA, Gariepy J, Schoolnik G, Murad F. Characterization of the receptor for heat-stable enterotoxin from Escherichia coli in rat intestine. J Biol Chem. 1986;261(3):1470–6. PubMed PMID: 3944095.

    CAS  PubMed  Google Scholar 

  • Lariviere S, Gyles CL, Barnum DA. A comparative study of the rabbit and pig gut loop systems for the assay of Escherichia coli enterotoxin. Can J Comp Med. 1972;36(4):319–28. PubMed PMID: 4263909; PubMed Central PMCID: PMCPMC1319692.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lazure C, Seidah NG, Chretien M, Lallier R, St-Pierre S. Primary structure determination of Escherichia coli heat-stable enterotoxin of porcine origin. Can J Biochem Cell Biol. 1983;61(5):287–92. PubMed PMID: 6349752.

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Zhang C, Mateo K, Nataro JP, Robertson DC, Zhang W. Modified heat-stable toxins (hSTa) of enterotoxigenic Escherichia coli lose toxicity but display antigenicity after being genetically fused to heat-labile toxoid LT(R192G). Toxins (Basel). 2011a;3(9):1146–62. doi:10.3390/toxins3091146. Epub 2011/11/10. PubMed PMID: 22069760; PubMed Central PMCID: PMC3202872.

    Article  CAS  Google Scholar 

  • Liu M, Ruan X, Zhang C, Lawson SR, Knudsen DE, Nataro JP, et al. Heat-labile- and heat-stable-toxoid fusions (LTR(1)(9)(2)G-STaP(1)(3)F) of human enterotoxigenic Escherichia coli elicit neutralizing antitoxin antibodies. Infect Immun. 2011b;79(10):4002–9. doi:10.1128/IAI.00165-11. PubMed PMID: 21788385; PubMed Central PMCID: PMC3187267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lockwood DE, Robertson DC. Development of a competitive enzyme-linked immunosorbent assay (ELISA) for Escherichia coli heat-stable enterotoxin (STa). J Immunol Methods. 1984;75(2):295–307. Epub 1984/12/31. PubMed PMID: 6520401.

    Article  CAS  PubMed  Google Scholar 

  • Lorntz B, Soares AM, Moore SR, Pinkerton R, Gansneder B, Bovbjerg VE, et al. Early childhood diarrhea predicts impaired school performance. Pediatr Infect Dis J. 2006;25(6):513–20. doi:10.1097/01.inf.0000219524.64448.90. PubMed PMID: 16732149.

    Article  PubMed  Google Scholar 

  • Lowenadler B, Lake M, Elmblad A, Holmgren E, Holmgren J, Karlstrom A, et al. A recombinant Escherichia coli heat-stable enterotoxin (STa) fusion protein eliciting anti-STa neutralizing antibodies. FEMS Microbiol Lett. 1991;66(3):271–7. PubMed PMID: 1769524.

    Article  CAS  PubMed  Google Scholar 

  • Lucas ML. A reconsideration of the evidence for Escherichia coli STa (heat stable) enterotoxin-driven fluid secretion: a new view of STa action and a new paradigm for fluid absorption. J Appl Microbiol. 2001;90(1):7–26. PubMed PMID: 11155118.

    Article  CAS  PubMed  Google Scholar 

  • Lucas ML. Amendments to the theory underlying Ussing chamber data of chloride ion secretion after bacterial enterotoxin exposure. J Theor Biol. 2005;234(1):21–37. doi:10.1016/j.jtbi.2004.11.005. PubMed PMID: 15721033.

    Article  CAS  PubMed  Google Scholar 

  • Lucas ML. Enterocyte chloride and water secretion into the small intestine after enterotoxin challenge: unifying hypothesis or intellectual dead end? J Physiol Biochem. 2008;64(1):69–88. PubMed PMID: 18663997.

    Article  CAS  PubMed  Google Scholar 

  • Lucas ML. Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof. Exp Physiol. 2010;95(4):479–84. doi:10.1113/expphysiol.2009.049437. PubMed PMID: 20233893.

    Article  PubMed  Google Scholar 

  • Mann EA, Jump ML, Wu J, Yee E, Giannella RA. Mice lacking the guanylyl cyclase C receptor are resistant to STa-induced intestinal secretion. Biochem Biophys Res Commun. 1997;239(2):463–6. doi:10.1006/bbrc.1997.7487. PubMed PMID: 9344852.

    Article  CAS  PubMed  Google Scholar 

  • Mezoff AG, Giannella RA, Eade MN, Cohen MB. Escherichia coli enterotoxin (STa) binds to receptors, stimulates guanyl cyclase, and impairs absorption in rat colon. Gastroenterology. 1992;102(3):816–22. Epub 1992/03/01. PubMed PMID: 1347028.

    Article  CAS  PubMed  Google Scholar 

  • Moon HW, Whipp SC, Engstrom GW, Baetz AL. Response of the rabbit ileal loop to cell-free products from Escherichia coli enteropathogenic for swine. J Infect Dis. 1970;121(2):182–7. PubMed PMID: 4905648.

    Article  CAS  PubMed  Google Scholar 

  • Moon HW, Baetz AL, Giannella RA. Immunization of swine with heat-stable Escherichia coli enterotoxin coupled to a carrier protein does not protect suckling pigs against an Escherichia coli strain that produces heat-stable enterotoxin. Infect Immun. 1983;39(2):990–2. PubMed PMID: 6339398; PubMed Central PMCID: PMCPMC348047.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moseley SL, Samadpour-Motalebi M, Falkow S. Plasmid association and nucleotide sequence relationships of two genes encoding heat-stable enterotoxin production in Escherichia coli H-10407. J Bacteriol. 1983a;156(1):441–3. PubMed PMID: 6352687; PubMed Central PMCID: PMCPMC215104.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moseley SL, Hardy JW, Hug MI, Echeverria P, Falkow S. Isolation and nucleotide sequence determination of a gene encoding a heat-stable enterotoxin of Escherichia coli. Infect Immun. 1983b;39(3):1167–74. PubMed PMID: 6341230; PubMed Central PMCID: PMCPMC348079.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mullan NA, Burgess MN, Newsome PM. Characterization of a partially purified methanol-soluble heat-stable Escherichia coli enterotoxin in infant mice. Infect Immun. 1978;19(3):779–84. PubMed PMID: 346484; PubMed Central PMCID: PMCPMC422256.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Murek M, Kopic S, Geibel J. Evidence for intestinal chloride secretion. Exp Physiol. 2010;95(4):471–8. doi:10.1113/expphysiol.2009.049445. PubMed PMID: 20233891.

    Article  CAS  PubMed  Google Scholar 

  • Nair GB, Takeda Y. The heat-stable enterotoxins. Microb Pathog. 1998;24(2):123–31. Epub 1998/04/16. PubMed PMID: 9480795.

    Article  CAS  PubMed  Google Scholar 

  • Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998;11(1):142–201. Epub 1998/02/11. PubMed PMID: 9457432; PubMed Central PMCID: PMC121379.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson YB, Pande D, McCormick J, Balloch KJ, Lucas ML. Lack of evidence in vivo for nitrergic inhibition by Escherichia coli (STa) enterotoxin of fluid absorption from rat proximal jejunum. J Physiol Biochem. 2007;63(3):231–7. PubMed PMID: 18309779.

    Article  CAS  PubMed  Google Scholar 

  • Niehaus MD, Moore SR, Patrick PD, Derr LL, Lorntz B, Lima AA, et al. Early childhood diarrhea is associated with diminished cognitive function 4 to 7 years later in children in a northeast Brazilian shantytown. Am J Trop Med Hyg. 2002;66(5):590–3. PubMed PMID: 12201596.

    Article  PubMed  Google Scholar 

  • Ogawa A, Kato J, Watanabe H, Nair BG, Takeda T. Cloning and nucleotide sequence of a heat-stable enterotoxin gene from Vibrio cholerae non-O1 isolated from a patient with traveler’s diarrhea. Infect Immun. 1990;58(10):3325–9. PubMed PMID: 2205577; PubMed Central PMCID: PMCPMC313657.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Takahara M. Synthesis of Escherichia coli heat-stable enterotoxin STp as a pre-pro form and role of the pro sequence in secretion. J Bacteriol. 1990;172(9):5260–5. PubMed PMID: 2203746; PubMed Central PMCID: PMCPMC213188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Okamoto K, Yukitake J, Kawamoto Y, Miyama A. Substitutions of cysteine residues of Escherichia coli heat-stable enterotoxin by oligonucleotide-directed mutagenesis. Infect Immun. 1987;55(9):2121–5. PubMed PMID: 3305364; PubMed Central PMCID: PMCPMC260666.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Okamoto K, Yukitake J, Miyama A. Reduction of enterotoxic activity of Escherichia coli heat-stable enterotoxin by substitution for an asparagine residue. Infect Immun. 1988;56(8):2144–8. PubMed PMID: 3294186; PubMed Central PMCID: PMCPMC259536.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Yukitake J, Okamoto K, Miyama A. Enterotoxicity and immunological properties of two mutant forms of Escherichia coli STIp with lysine or arginine substituted for the asparagine residue at position 11. FEMS Microbiol Lett. 1992;77(1–3):191–6. PubMed PMID: 1459408.

    Article  CAS  PubMed  Google Scholar 

  • Ostedgaard LS, Baldursson O, Welsh MJ. Regulation of the cystic fibrosis transmembrane conductance regulator Cl- channel by its R domain. J Biol Chem. 2001;276(11):7689–92. doi:10.1074/jbc.R100001200. PubMed PMID: 11244086.

    Article  CAS  PubMed  Google Scholar 

  • Ozaki H, Sato T, Kubota H, Hata Y, Katsube Y, Shimonishi Y. Molecular structure of the toxin domain of heat-stable enterotoxin produced by a pathogenic strain of Escherichia coli. A putative binding site for a binding protein on rat intestinal epithelial cell membranes. J Biol Chem. 1991;266(9):5934–41. Epub 1991/03/25. PubMed PMID: 2005130.

    CAS  PubMed  Google Scholar 

  • Pereira CM, Guth BE, Sbrogio-Almeida ME, Castilho BA. Antibody response against Escherichia coli heat-stable enterotoxin expressed as fusions to flagellin. Microbiology. 2001;147(Pt 4):861–7. doi:10.1099/00221287-147-4-861. PubMed PMID: 11283282.

    Article  CAS  PubMed  Google Scholar 

  • Picken RN, Mazaitis AJ, Maas WK, Rey M, Heyneker H. Nucleotide sequence of the gene for heat-stable enterotoxin II of Escherichia coli. Infect Immun. 1983;42(1):269–75. PubMed PMID: 6352496; PubMed Central PMCID: PMCPMC264554.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pugsley AP. The complete general secretory pathway in gram-negative bacteria. Microbiol Rev. 1993;57(1):50–108. PubMed PMID: 8096622; PubMed Central PMCID: PMCPMC372901.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rao MC, Guandalini S, Smith PL, Field M. Mode of action of heat-stable Escherichia coli enterotoxin. Tissue and subcellular specificities and role of cyclic GMP. Biochim Biophys Acta. 1980;632(1):35–46. PubMed PMID: 6106508.

    Article  CAS  PubMed  Google Scholar 

  • Rao MC, Orellana SA, Field M, Robertson DC, Giannella RA. Comparison of the biological actions of three purified heat-stable enterotoxins: effects on ion transport and guanylate cyclase activity in rabbit ileum in vitro. Infect Immun. 1981;33(1):165–70. Epub 1981/07/01. PubMed PMID: 6114927; PubMed Central PMCID: PMC350671.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rasheed JK, Guzman-Verduzco LM, Kupersztoch YM. Two precursors of the heat-stable enterotoxin of Escherichia coli: evidence of extracellular processing. Mol Microbiol. 1990;4(2):265–73. PubMed PMID: 2187146.

    Article  CAS  PubMed  Google Scholar 

  • Rausch D, Ruan X, Nandre R, Duan Q, Hashish E, Casey TA, et al. Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC). Vet Microbiol. 2016. doi:10.1016/j.vetmic.2016.02.002. PubMed PMID: 26878972.

    PubMed  Google Scholar 

  • Robertson DC, Dreyfus LA, Frantz JC. Chemical and immunological properties of Escherichia coli heat-stable enterotoxin. Prog Food Nutr Sci. 1983;7(3–4):147–56. Epub 1983/01/01. PubMed PMID: 6686335.

    CAS  PubMed  Google Scholar 

  • Rolfe V, Levin RJ. Enterotoxin Escherichia coli STa activates a nitric oxide-dependent myenteric plexus secretory reflex in the rat ileum. J Physiol. 1994;475(3):531–7. PubMed PMID: 8006834; PubMed Central PMCID: PMCPMC1160403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ronnberg B, Carlsson J, Wadstrom T. Development of an enzyme-linked immunosorbent assay for detection of Escherichia coli heat-stable enterotoxin. FEMS Microbiol Lett. 1984;23(1984):275–9.

    Article  Google Scholar 

  • Ruan X, Robertson DC, Nataro JP, Clements JD, Zhang W, The STa Toxoid Vaccine Consortium Group. Characterization of heat-stable (STa) toxoids of enterotoxigneic Escherichia coli fused to a double mutant heat-labile toxin (dmLT) peptide in inducing neutralizing anti-STa antibodies. Infect Immun. 2014;82:1823.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saarilahti HT, Palva ET, Holmgren J, Sanchez J. Fusion of genes encoding Escherichia coli heat-stable enterotoxin and outer membrane protein OmpC. Infect Immun. 1989;57(11):3663–5. PubMed PMID: 2680976; PubMed Central PMCID: PMCPMC259882.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sack RB. The epidemiology of diarrhea due to enterotoxigenic Escherichia coli. J Infect Dis. 1978;137(5):639–40. Epub 1978/05/01. PubMed PMID: 351078.

    Article  CAS  PubMed  Google Scholar 

  • Sack DA, Merson MH, Wells JG, Sack RB, Morris GK. Diarrhoea associated with heat-stable enterotoxin-producing strains of Escherichia coli. Lancet. 1975;2(7928):239–41. Epub 1975/08/09. PubMed PMID: 49793.

    Article  CAS  PubMed  Google Scholar 

  • Sack DA, Shimko J, Torres O, Bourgeois AL, Francia DS, Gustafsson B, et al. Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. coli diarrhoea of travellers to Guatemala and Mexico. Vaccine. 2007;25(22):4392–400. doi:10.1016/j.vaccine.2007.03.034. Epub 2007/04/24. PubMed PMID: 17448578.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez J, Uhlin BE, Grundstrom T, Holmgren J, Hirst TR. Immunoactive chimeric ST-LT enterotoxins of Escherichia coli generated by in vitro gene fusion. FEBS Lett. 1986;208(2):194–8. Epub 1986/11/24. PubMed PMID: 2430831.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez J, Hirst TR, Uhlin BE. Hybrid enterotoxin LTA::STa proteins and their protection from degradation by in vivo association with B-subunits of Escherichia coli heat-labile enterotoxin. Gene. 1988a;64(2):265–75. Epub 1988/04/29. PubMed PMID: 2841198.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez J, Svennerholm AM, Holmgren J. Genetic fusion of a non-toxic heat-stable enterotoxin-related decapeptide antigen to cholera toxin B-subunit. FEBS Lett. 1988b;241(1–2):110–4. Epub 1988/12/05. PubMed PMID: 3058509.

    Article  CAS  PubMed  Google Scholar 

  • Sanders JW, Putnam SD, Riddle MS, Tribble DR. Military importance of diarrhea: lessons from the Middle East. Curr Opin Gastroenterol. 2005;21(1):9–14. Epub 2005/02/03. PubMed PMID: 15687878.

    PubMed  Google Scholar 

  • Sato T, Ozaki H, Hata Y, Kitagawa Y, Katsube Y, Shimonishi Y. Structural characteristics for biological activity of heat-stable enterotoxin produced by enterotoxigenic Escherichia coli: X-ray crystallography of weakly toxic and nontoxic analogs. Biochemistry. 1994;33(29):8641–50. PubMed PMID: 8038153.

    Article  CAS  PubMed  Google Scholar 

  • Schulz S, Green CK, Yuen PS, Garbers DL. Guanylyl cyclase is a heat-stable enterotoxin receptor. Cell. 1990;63(5):941–8. PubMed PMID: 1701694.

    Article  CAS  PubMed  Google Scholar 

  • Schulz S, Lopez MJ, Kuhn M, Garbers DL. Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice. J Clin Invest. 1997;100(6):1590–5. doi:10.1172/JCI119683. PubMed PMID: 9294128; PubMed Central PMCID: PMCPMC508341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sears CL, Kaper JB. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev. 1996;60(1):167–215. PubMed PMID: 8852900; PubMed Central PMCID: PMCPMC239424.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sekizaki T, Akashi H, Terakado N. Nucleotide sequences of the genes for Escherichia coli heat-stable enterotoxin I of bovine, avian, and porcine origins. Am J Vet Res. 1985;46(4):909–12. PubMed PMID: 2990268.

    CAS  PubMed  Google Scholar 

  • Sha J, Kozlova EV, Chopra AK. Role of various enterotoxins in Aeromonas hydrophila-induced gastroenteritis: generation of enterotoxin gene-deficient mutants and evaluation of their enterotoxic activity. Infect Immun. 2002;70(4):1924–35. doi:10.1128/Iai.70.4.1924-1935.2002. PubMed PMID: WOS:000174573200029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimomura H, Dangott LJ, Garbers DL. Covalent coupling of a resact analogue to guanylate cyclase. J Biol Chem. 1986;261(33):15778–82. PubMed PMID: 2877982.

    CAS  PubMed  Google Scholar 

  • Shimonishi Y, Hidaka Y, Koizumi M, Hane M, Aimoto S, Takeda T, et al. Mode of disulfide bond formation of a heat-stable enterotoxin (STh) produced by a human strain of enterotoxigenic Escherichia coli. FEBS Lett. 1987;215(1):165–70. PubMed PMID: 3552731.

    Article  CAS  PubMed  Google Scholar 

  • So M, McCarthy BJ. Nucleotide sequence of the bacterial transposon Tn1681 encoding a heat-stable (ST) toxin and its identification in enterotoxigenic Escherichia coli strains. Proc Natl Acad Sci U S A. 1980;77(7):4011–5. PubMed PMID: 6254008; PubMed Central PMCID: PMCPMC349758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Svennerholm AM, Holmgren J. Immunity to enterotoxin-producing bacteria. In: MacDonald TT, editor. Immunology of gastrointestinal diseases. Dordrecht: Kluwer; 1992. p. 227–46.

    Chapter  Google Scholar 

  • Svennerholm AM, Holmgren J. Oral B-subunit whole-cell vaccines against cholera and enterotoxigenic Escherichia coli diarrhoea. In: Ala’Aldeen DAA, Hormaeche CE, editors. Molecular and clinical aspects of bacterial vaccine development. Chichester: Wiley; 1995. p. 205–32.

    Google Scholar 

  • Svennerholm A-M, Lindblad M, Svennerholm B, Holmgren J. Synthesis of nontoxic, antibody-binding Escherichia coli heat-stable enterotoxin (STa) peptides. FEMS Microbiol Lett. 1988;55(1):23–8.

    Article  CAS  Google Scholar 

  • Takao T, Hitouji T, Aimoto S, Shimonishi Y, Hara S, Takeda T, et al. Amino acid sequence of a heat-stable enterotoxin isolated from enterotoxigenic Escherichia coli strain 18D. FEBS Lett. 1983;152(1):1–5. PubMed PMID: 6341083.

    Article  CAS  PubMed  Google Scholar 

  • Takao T, Tominaga N, Yoshimura S, Shimonishi Y, Hara S, Inoue T, et al. Isolation, primary structure and synthesis of heat-stable enterotoxin produced by Yersinia enterocolitica. Eur J Biochem/FEBS. 1985;152(1):199–206. PubMed PMID: 4043080.

    Article  CAS  Google Scholar 

  • Takeda T, Nair GB, Suzuki K, Zhe HX, Yokoo Y, De Mol P, et al. Epitope mapping and characterization of antigenic determinants of heat-stable enterotoxin (STh) of enterotoxigenic Escherichia coli by using monoclonal antibodies. Infect Immun. 1993;61(1):289–94. PubMed PMID: 7678100; PubMed Central PMCID: PMCPMC302717.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Taxt AM, Diaz Y, Aasland R, Clements JD, Nataro JP, Sommerfelt H, et al. Towards rational design of a toxoid vaccine against the heat-stable toxin of Escherichia coli. Infect Immun. 2016;84(4):1239–49. doi:10.1128/IAI.01225-15. PubMed PMID: 26883587; PubMed Central PMCID: PMCPMC4807477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson MR, Giannella RA. Revised amino acid sequence for a heat-stable enterotoxin produced by an Escherichia coli strain (18D) that is pathogenic for humans. Infect Immun. 1985;47(3):834–6. PubMed PMID: 3882570; PubMed Central PMCID: PMCPMC261404.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson MR, Jordan RL, Luttrell MA, Brandwein H, Kaper JB, Levine MM, et al. Blinded, two-laboratory comparative analysis of Escherichia coli heat-stable enterotoxin production by using monoclonal antibody enzyme-linked immunosorbent assay, radioimmunoassay, suckling mouse assay, and gene probes. J Clin Microbiol. 1986;24(5):753–8. PubMed PMID: 3533986.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Turvill JL, Kasapidis P, Farthing MJ. The sigma ligand, igmesine, inhibits cholera toxin and Escherichia coli enterotoxin induced jejunal secretion in the rat. Gut. 1999;45(4):564–9. PubMed PMID: 10486366; PubMed Central PMCID: PMCPMC1727666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaandrager AB, Schulz S, De Jonge HR, Garbers DL. Guanylyl cyclase C is an N-linked glycoprotein receptor that accounts for multiple heat-stable enterotoxin-binding proteins in the intestine. J Biol Chem. 1993a;268(3):2174–9. PubMed PMID: 8093618.

    CAS  PubMed  Google Scholar 

  • Vaandrager AB, van der Wiel E, de Jonge HR. Heat-stable enterotoxin activation of immunopurified guanylyl cyclase C. Modulation by adenine nucleotides. J Biol Chem. 1993b;268(26):19598–603. PubMed PMID: 8103520.

    CAS  PubMed  Google Scholar 

  • Vaandrager AB, Bot AG, De Jonge HR. Guanosine 3′,5′-cyclic monophosphate-dependent protein kinase II mediates heat-stable enterotoxin-provoked chloride secretion in rat intestine. Gastroenterology. 1997a;112(2):437–43. PubMed PMID: 9024297.

    Article  CAS  PubMed  Google Scholar 

  • Vaandrager AB, Tilly BC, Smolenski A, Schneider-Rasp S, Bot AG, Edixhoven M, et al. cGMP stimulation of cystic fibrosis transmembrane conductance regulator Cl- channels co-expressed with cGMP-dependent protein kinase type II but not type Ibeta. J Biol Chem. 1997b;272(7):4195–200. PubMed PMID: 9020133.

    Article  CAS  PubMed  Google Scholar 

  • Vaandrager AB, Smolenski A, Tilly BC, Houtsmuller AB, Ehlert EM, Bot AG, et al. Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation. Proc Natl Acad Sci U S A. 1998;95(4):1466–71. PubMed PMID: 9465038; PubMed Central PMCID: PMCPMC19047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaandrager AB, Bot AG, Ruth P, Pfeifer A, Hofmann F, De Jonge HR. Differential role of cyclic GMP-dependent protein kinase II in ion transport in murine small intestine and colon. Gastroenterology. 2000;118(1):108–14. PubMed PMID: 10611159.

    Article  CAS  PubMed  Google Scholar 

  • Waldman SA, O’Hanley P, Falkow S, Schoolnik G, Murad F. A simple, sensitive, and specific assay for the heat-stable enterotoxin of Escherichia coli. J Infect Dis. 1984;149(1):83–9. PubMed PMID: 6141207.

    Article  CAS  PubMed  Google Scholar 

  • Weiglmeier PR, Rosch P, Berkner H. Cure and curse: E. coli heat-stable enterotoxin and its receptor guanylyl cyclase C. Toxins (Basel). 2010;2(9):2213–29. doi:10.3390/toxins2092213. PubMed PMID: 22069681; PubMed Central PMCID: PMCPMC3153297.

    Article  CAS  Google Scholar 

  • WHO. Future directions for research on enterotoxigenic Escherichia coli vaccines for developing countries. Wkly Epidemiol Rec. 2006;81:97–107.

    Google Scholar 

  • Yamanaka H, Fuke Y, Hitotsubashi S, Fujii Y, Okamoto K. Functional properties of pro region of Escherichia coli heat-stable enterotoxin. Microbiol Immunol. 1993;37(3):195–205. PubMed PMID: 7686611.

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka H, Kameyama M, Baba T, Fujii Y, Okamoto K. Maturation pathway of Escherichia coli heat-stable enterotoxin I: requirement of DsbA for disulfide bond formation. J Bacteriol. 1994;176(10):2906–13. PubMed PMID: 8188592; PubMed Central PMCID: PMCPMC205446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanaka H, Nomura T, Fujii Y, Okamoto K. Need for TolC, an Escherichia coli outer membrane protein, in the secretion of heat-stable enterotoxin I across the outer membrane. Microb Pathog. 1998;25(3):111–20. doi:10.1006/mpat.1998.0211. PubMed PMID: 9790870.

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki S, Ito H, Hirayama T, Takeda Y, Shimonishi Y. Effects on the activity of amino acids replacement at positions 12, 13, and 14 heat-stable enterotoxin (STh) by chemical synthesis. In: 24th Joint Conference on the US-Japan Cooperative Medical Science Program on Cholera and Related Diarrheal Disease Panel; Tokyo. 1988. p. p42.

    Google Scholar 

  • Yamasaki S, Sato T, Hidaka Y, Ozaki H, Ito H, Hirayama T, et al. Structure-activity relationship of Escherichia coli heat-stable enterotoxin – role of Ala residue at position-14 in toxin-receptor interaction. Bull Chem Soc Jpn. 1990;63(7):2063–70. doi:10.1246/bcsj.63.2063. PubMed PMID: WOS:A1990DQ80300034.

    Article  CAS  Google Scholar 

  • Yang Y, Gao Z, Guzman-Verduzco LM, Tachias K, Kupersztoch YM. Secretion of the STA3 heat-stable enterotoxin of Escherichia coli: extracellular delivery of Pro-STA is accomplished by either Pro or STA. Mol Microbiol. 1992;6(23):3521–9. PubMed PMID: 1474896.

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura S, Miki M, Ikemura H, Aimoto S, Shimonishi Y, Takeda T, et al. Chemical synthesis of a heat-stable entero-toxin produced by entero-toxigenic Escherichia coli strain-18d. Bull Chem Soc Jpn. 1984;57(1):125–33. doi:10.1246/bcsj.57.125. PubMed PMID: WOS:A1984SE47300023.

    Article  CAS  Google Scholar 

  • Yoshimura S, Ikemura H, Watanabe H, Aimoto S, Shimonishi Y, Hara S, et al. Essential structure for full enterotoxigenic activity of heat-stable enterotoxin produced by enterotoxigenic Escherichia coli. FEBS Lett. 1985;181(1):138–42. Epub 1985/02/11. PubMed PMID: 3972100.

    Article  CAS  PubMed  Google Scholar 

  • Yoshino K, Takao T, Huang X, Murata H, Nakao H, Takeda T, et al. Characterization of a highly toxic, large molecular size heat-stable enterotoxin produced by a clinical isolate of Yersinia enterocolitica. FEBS Lett. 1995;362(3):319–22. PubMed PMID: 7729521.

    Article  CAS  PubMed  Google Scholar 

  • Young A, Levin RJ. Segmental heterogeneity of rat colonic electrogenic secretion in response to the bacterial enterotoxin Escherichia coli STa in vitro. Exp Physiol. 1991;76(6):979–82. PubMed PMID: 1768420.

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Sack DA. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines. 2012;11(6):677–94. doi:10.1586/erv.12.37. PubMed PMID: 22873126.

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Zhang W. Escherichia coli K88ac fimbriae expressing heat-labile and heat-stable (STa) toxin epitopes elicit antibodies that neutralize cholera toxin and STa toxin and inhibit adherence of K88ac fimbrial E. coli. Clin Vaccine Immunol. 2010;17(12):1859–67. doi:10.1128/CVI.00251-10. Epub 2010/10/29. PubMed PMID: 20980482; PubMed Central PMCID: PMC3008177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Robertson DC, Zhang C, Bai W, Zhao M, Francis DH. Escherichia coli constructs expressing human or porcine enterotoxins induce identical diarrheal diseases in a piglet infection model. Appl Environ Microbiol. 2008;74(18):5832–7. doi:10.1128/AEM.00893-08. Epub 2008/07/29. PubMed PMID: 18658289; PubMed Central PMCID: PMC2547035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Zhang C, Francis DH, Fang Y, Knudsen D, Nataro JP, et al. Genetic fusions of heat-labile (LT) and heat-stable (ST) toxoids of porcine enterotoxigenic Escherichia coli elicit neutralizing anti-LT and anti-STa antibodies. Infect Immun. 2010;78(1):316–25. doi:10.1128/IAI.00497-09. Epub 2009/10/28. PubMed PMID: 19858307; PubMed Central PMCID: PMC2798211.

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Knudsen DE, Liu M, Robertson DC, Zhang W, The STa Toxoid Vaccine Consortium Group. Toxicity and immunogenicity of enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTaA14Q-LTS63K/R192G/L211A in a murine model. PLoS One. 2013;8(10):e77386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Diagnostic Medicine/Pathobiology, Kansas State University College of Veterinary Medicine, 1800 Denison Avenue, Manhattan, KS, USA

    Qiangde Duan & Weiping Zhang

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  1. Qiangde Duan
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  1. Biology Department, Wilson College, Chambersburg, Pennsylvania, USA

    Brad Stiles

  2. Department of Biochemistry, School of Medicine and Instituto Clodomiro Picado, Faculty of Microbiology, University of Costa Rica, San Pedro de Montes de Oca, Costa Rica

    Alberto Alape-Girón

  3. Department of Pathology and Microbiology, Université de Montréal, Saint-Hyacinthe, Québec, Canada

    J. Daniel Dubreuil

  4. College of Pharmacy, Roseman University of Health Sciences, Henderson, Nevada, USA

    Manas Mandal

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Duan, Q., Zhang, W. (2018). Structure, Enterotoxicity, and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Stable Type I Toxin (STa) and Derivatives. In: Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6449-1_31

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