Chapter 11 : Toxins of

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This chapter reviews new information about cholera enterotoxin (CT) and about recently discovered toxins produced by . The single tryptophan residue (Trp-88) in each subunit is essential for binding, as shown by chemical modification and site-directed mutagenesis studies. The majority of the experiments described in the chapter have been performed in vivo, and the results often differ from those obtained in in vitro experiments examining the role of the enteric nervous system (ENS). Several additional toxins produced by are discussed, such as hemolysin-cytolysin, zonula occludens toxin (Zot), accessory cholera enterotoxin and miscellaneous toxins. Stable enterotoxin (ST) and thermostable direct hemolysin (TDH), have well-established mechanisms of enterotoxicity but are rarely produced by . Two of the toxins, the sodium channel inhibitor and the "new cholera toxin" (NCT) of Sanyal and coworkers, are insufficiently characterized to access their potential roles in disease. The three non-CT toxins that are the best characterized are the hemolysin-cytolysin, Zot, and Ace. The study of CT has produced profound insights into the pathogenesis, treatment, and prevention of cholera. Furthermore, it has yielded knowledge on basic cellular functions and structures such as intracellular messengers and neurological pathways. The study of toxins other than CT has demonstrated new potential mechanisms of diarrhea and may also produce new insights into basic cellular functions such as the assembly and regulation of tight junctions.

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Image of Figure 1
Figure 1

Crystal structure of the LT holotoxin shown as a ribbon plot. The A subunit shown at the top is connected to the В pentamer via the long helical structure of the A peptide. Reprinted from with permission ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Image of Figure 2
Figure 2

(A) Ribbon plot of the structure of the LT A subunit showing the triangular shape of the A peptide (top right) and the long helix (left) of A, terminated by a single small helix and tail. (B) Schematic secondary structure diagram of the В pentamer. A single В subunit is shown in light gray. Reprinted from with permission ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 3

Mode of action of CT; see text for details. (A) Adenylate cyclase, located in the basolateral membrane of intestinal epithelial cells, is regulated by G proteins. CT binds via the B-subunit pentamer to the GM ganglioside receptor inserted into the lipid bilayer. (B) The A subunit enters the cell, perhaps via endosomes, and is proteolytically cleaved, with subsequent reduction of the disulfide bond to yield A and A peptides. The A peptide is activated (at least in vitro) by ARF and transfers an ADP-ribose moiety (ADPR) and NAD to the subunit of the G protein. The ADP-ribosylated subunit dissociates from the other subunits of G and activates adenylate cyclase, thereby increasing the intracellular сAMP concentration. Three possible scenarios have been proposed to explain entry of the toxin and activation of adenylate cyclase. Possibility 1 proposes that the A subunit translocates through the apical membrane, leaving the В pentamer on the apical membrane. The A diffuses freely through the cytoplasm to the basolateral membrane, where it ADP-ribosylates G . Possibility 2 is that the A peptide ADP-ribosylates an subunit in the apical membrane. The ADP-ribosylated subunit traverses the cell to attach to the adenylate cyclase located in the basolateral membrane. Possibility 3 is that the entire toxin enters the cell via endosomes and the A subunit translocates through the endosomal membrane. The endosome travels through the cell with the A peptide still associated with the endosomal membrane. The A peptide ADP-ribosylates the G, located in the basolateral membrane, perhaps after an endosome-plasma membrane fusion. (C) Increased cAMP activates protein kinase A, leading to protein phosphorylation. Protein phosphorylation leads to increased Cl secretion in crypt cells and decreased NaCl-coupled absorption in villus cells.

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 4

Arrangement of and genes in the core region. RS1 elements are shown on both sides of the core region, a common arrangement in El Tor but not classical strains. The enlarged regions depict the overlapping open reading frames of and and of and . In addition, the region where the stop codon of overlaps the first ToxR binding repeat upstream of the operon is also enlarged. Also shown are an open reading frame of unknown function, and (core-encoded pilus), the gene for a recently described colonization factor ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 5

Electron micrograph showing the entry of wheat germ agglutinin-horseradish peroxidase into the para-cellular space of rabbit ileal cells exposed for 60 min to medium (A) or to culture supernatants of Zot CVD101 (B). Taken from Fasano et al. ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 6

Freeze-fracture studies of rabbit ileal tissue showing effect of culture supernatants of on ZO. (A) An intact ZO with numerous intersections (arrowheads) between junctional strands. MV, microvilli. (B) An affected ZO from ileal tissue exposed to culture supernatants of 395. Taken from Fasano et al. ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 7

Amino acid sequence comparison of the predicted ace gene product and predicted sequence of two ion-transporting ATPases, the human plasma membrane Ca pump (CaPM) and the Ca-transporting ATPase from rat brain (RPMCA); a virulence protein in (SpvB); and the CF transmembrane conductance regulator (CFTR). Boxes indicate identical or similar amino acid residues in Ace and the other sequences. Ace was aligned separately with CFTR to maximize sequence similarity. Taken from Trucksis et al. ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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Figure 8

Potential amphipathic region of Ace. The C-terminal end of the Ace protein containing a predicted a helix is arranged in the form of a wheel to show the predominance of hydrophobic (boxed) residues on one side of the helix. The glutamine (Q) at the top of the wheel is residue 76 of the predicted amino acid sequence of Ace. Taken from Trucksis et al. ( ).

Citation: Kaper J, Fasano A, Trucksis M. 1994. Toxins of , p 145-176. In Wachsmuth I, Blake P, Olsvik Ø (ed), and Cholera. ASM Press, Washington, DC. doi: 10.1128/9781555818364.ch11
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1. Alm, R. A.,, G. Mayrhofer,, I. Kotlarski,, and P. A. Manning. 1991. Amino-terminal domain of the El Tor haemolysin of Vibrio cholerae O1 is expressed in classical strains and is cytotoxic. Vaccine 9: 588 594.
2. Alm, R. A.,, U. H. Stroeher,, and P. A. Manning. 1988. Extracellular proteins of Vibrio cholerae: nucleotide sequence of the structural gene ( hlyA) for the haemolysin of the haemolytic El Tor strain 017 and characterization of the hlyA mutation in the non-haemolytic classical strain 569B. Mol. Microbiol. 2: 481 488.
3. Amiranoff, B.,, M. Laburthe,, and G. Rosselin. 1980. Characterization of specific binding sites for vasoactive intestinal peptide in intestinal epithelial cell membranes. Biochim. Biophys. Acta 627: 215 224.
4. Atisook, K.,, S. Carson,, and J. L. Madara. 1990. Effects of phlorizin and sodium on glucose-elicited alterations of cell junctions in intestinal epithelia. Am. J. Physiol. 258: C77 C85.
5. Atisook, K.,, and J. L. Madara. 1991. An oligopeptide permeates intestinal tight junctions at glucose-elicited dilatations. Gastroenterology 100: 719 724.
6. Baudry, B.,, A. Fasano,, J. Ketley,, and J. B. Kaper. 1992. Cloning of a gene ( zot) encoding a new toxin produced by Vibrio cholerae. Infect. Immun. 60: 428 434.
7. Bear, C. E.,, C. Li,, N. Kartner,, R. J. Bridges,, T. J. Jensen,, M. Ramjeesingh,, and J. R. Riordan. 1992. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell 68: 809 818.
8.Bennett, A. 1971. Cholera and prostaglandins. Nature (London) 231: 536.
9. Berschneider, H. M.,, M. R. Knowles,, R. G. Azizkhan,, R. C. Boucher,, N. A. Tobey,, R. C. Orlando,, and D. W. Powell. 1988. Altered intestinal chloride transport in cystic fibrosis. FASEB J. 2: 2625 2629.
10. Beubler, E.,, G. Rollar,, A. Saria,, K. Bukhave,, and J. Rask-Madsen. 1989. Involvement of 5-hydroxytryptamine, prostaglandin E 2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of the rat in vivo. Gastroenterology 96: 368 376.
11. Booth, I. W.,, M. M. Levine,, and J. T. Harries. 1984. Oral rehydration therapy in acute diarrhoea in childhood. J. Pediatr. Gastroenterol. Nutr. 3: 491 499.
12. Bromander, A.,, J. Holmgren,, and N. Lycke. 1991. Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro. J. Immunol. 146: 2908 2914.
13. Brown, M. H.,, and P. A. Manning. 1985. Haemolysin genes of Vibrio cholerae: presence of homologous DNA in non-haemolytic O1 and haemolytic non-O1 strains. FEMS Microbiol. Lett. 30: 197 201.
14. Burch, R. M.,, C. Jelsema,, and J. Axelrod. 1988. Cholera toxin and pertussis toxin stimulate prostaglandin Ej synthesis in a murine macrophage cell line. J. Pharmacol. Exp. Ther. 244: 765 773.
15. Carey, H. V.,, and H. J. Cooke. 1986. Submucosal nerves and cholera toxin-induced secretion in guinea pig ileum in vitro. Digest. Dis. Sci. 31: 732 736.
16. Cassel, D.,, and Z. Selinger. 1977. Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc. Natl. Acad. Sci. USA 74: 3307 3311.
17. Cassuto, J.,, J. Fahrenkrug,, M. Jodal,, R. Tut-tle,, and O. Lundgren. 1981. The release of vasoactive intestinal polypeptide from the cat small intestine exposed to cholera toxin. Gut 22: 958 963.
18. Cassuto, J.,, M. Jodal,, and O. Lundgren. 1982. The effect of nicotinic and muscarinic receptor blockade on cholera toxin induced intestinal secretion in rats and cats. Acta Physiol. Scand. 114: 573 577.
19. Cassuto, J.,, M. Jodal,, R. Tuttle,, and O. Lundgren. 1981. On the role of intramural nerves in the pathogenesis of cholera toxin-induced intestinal secretion. Scand. J. Gastroenterol. 16: 377 384.
20. Cassuto, J.,, A. Siewert,, M. Jodal,, and O. Lundgren. 1983. The involvement of intramural nerves in cholera toxin induced intestinal secretion. Acta Physiol. Scand. 117: 195 202.
21. Chang, E. B.,, and M. C. Rao,. 1991. Intracellular mediators of intestinal electrolyte transport, p. 49 72. In M. Field (ed.), Diarrheal Diseases. Elsevier, New York.
22. Chaudhary, V. K.,, Y. Jinno,, D. Fitzgerald,, and I. Pastan. 1990. Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxicity. Proc. Natl. Acad. Sci. USA 87: 308 312.
23. Comstock, L.,, and J. B. Kaper. Unpublished data.
24. Cooke, H. J., 1991. Hormones and neurotransmitters regulating intestinal ion transport, p. 23 48. In M. Field (ed.), Diarrheal Diseases. Elsevier, New York.
25. Czerkinsky, C.,, M. W. Russell,, N. Lycke,, M. Lindblad,, and J. Holmgren. 1989. Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramuscosal tissues. Infect. Immun. 57: 1072 1077.
26. De, S. N. 1959. Enterotoxicity of bacteria-free culture filtrate of Vibrio cholerae. Nature (London) 183: 1533 1534.
27. de Jonge, H. R., 1991. Intracellular mechanisms regulating intestinal secretion, p. 107 114. In T. Wadström,, P. H. Mäkelä,, A.-M. Svennerholm,, and H. Wolf-Waltz (ed.), Molecular Pathogenesis of Gastrointestinal Infections. Plenum Press, New York.
28. Dertzbaugh, M. T.,, D. L. Peterson,, and F. L. Macrina. 1990. Cholera toxin B-subunit gene fusion: structural and functional analysis of the chimeric protein. Infect. Immun. 58: 70 79.
29. De Wolf, M. J. S.,, M. Fridkin,, M. M. Epstein, andL. D. Kohn. 1981. Structure-function studies of cholera toxin and its A protomers and B protomers—modification of tryptophan residues. J. Biol. Chem. 256: 5481 5488.
30. De Wolf, M. S. J.,, M. Fridkin,, and L. D. Kohn. 1981. Tryptophan residues of cholera toxin and its A protomers and B protomers. Intrinsic fluorescence and solute quenching upon interacting with the ganglioside GM 1, oligo-GM 1, or dansylated oligo-GM 1. J. Biol. Chem. 256: 5489 5496.
31. Diamond, J. M. 1977. The epithelial junction: bridge, gate and fence. Physiologist 20: 10 18.
32. Dominguez, P.,, G. Velasco,, F. Barros,, and P. S. Lozo. 1987. Intestinal brush border membranes contain regulatory subunits of adenylyl cyclase. Proc. Natl. Acad. Sci. USA 84: 6965 6969.
33. Dove, C. H.,, S. Z. Wang,, S. B. Price,, C. J. Phelps,, D. M. Lyerly,, T. D. Wilkens,, and J. L. Johnson. 1990. Molecular characterization of the Clostridium difficile toxin A gene. Infect. Immun. 58: 480 488.
34. Dubey, R. S.,, M. Lindblad,, and J. Holmgren. 1990. Purification of El Tor cholera enterotoxins and comparisons with classical toxin. J. Gen. Microbiol. 136: 1839 1847.
35. Duffey, M. E.,, B. Hainou,, S. Ho,, and C. J. Bentzel. 1981. Regulation of epithelial tight junction permeability by cyclic AMP. Nature (London) 294: 451 453.
36. Dutta, N. K.,, M. W. Panse,, and D. R. Kulkarni. 1959. Role of cholera toxin in experimental cholera. J. Bacteriol. 78: 594 595.
37. Farques, S. M.,, J. B. Kaper,, and M. J. Albert. Unpublished data.
38. Fasano, A.,, B. Baudry,, D. W. Pumplin,, S. S. Wasserman,, B. D. Tall,, J. M. Ketley,, and J. B. Kaper. 1991. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc. Natl. Acad. Sci. USA 88: 5242 5246.
39. Field, M. 1971. Intestinal secretion: effect of cyclic AMP and its role in cholera. N. Engl. J. Med. 284: 1137 1144.
40. Field, M., 1981. Secretion of electrolytes and water by mammalian small intestine, p. 963& 982. In L. R. Johnson (ed.), Physiology of the Gastrointestinal Tract. Raven Press, New York.
41. Field, M.,, D. Fromm,, Q. Al-Awqati,, and W. B. Greenough III. 1972. Effect of cholera enterotoxin on ion transport across isolated ileal mucosa. J. Clin. Invest. 51: 796 804.
42. Field, M.,, D. Fromm,, C. K. Wallace,, and W. B. Greenough III. 1969. S timulation of active chloride secretion in small intestine by cholera exotoxin. J. Clin. Invest. 48: 24a.
43. Field, M.,, M. C. Rao,, and E. B. Chang. 1989. Intestinal electrolyte transport and diarrheal disease. Part 2. N. Engl. J. Med. 321: 879 883.
44. Finkelstein, R. A., 1992. Cholera enterotoxin (choleragen)—a historical perspective, p. 155 187. In D. Barua, and W. B. Greenough III (eds.), Cholera. Plenum Medical Book Co., New York.
45. Finkelstein, R. A.,, M. Boesman-Finkelstein,, Y. Chang,, and C. C. Häse. 1992. Vibrio cholerae hemagglutinin/protease, colonial variation, virulence, and detachment. Infect. Immun. 60: 472 478.
46. Finkelstein, R. A.,, M. Boesman-Finkelstein,, and P. Holt. 1983. Vibrio cholerae hemagglutinin/lectin/protease hydrolyzes fibronectin and ovomucin: EM. Burnet revisited. Proc. Natl. Acad. Sci. USA 80: 1092 1095.
47. Finkelstein, R. A.,, M. F. Burks,, A. Zupan,, W. S. Dallas,, C. O. Jacob,, and D. S. Ludwig. 1987. Epitopes of the cholera family of enterotoxins. Rev. Infec. Dis. 9: 544 561.
48. Finkelstein, R. A.,, and J. J. LoSpalluto. 1969. Pathogenesis of experimental cholera: preparation and isolation of choleragen and choleragenoid. J. Exp. Med. 130: 185 202.
49. Francis, M. L.,, J. Ryan,, M. G. Jobling,, R. K. Holmes,, J. Moss,, and J. J. Mond. 1992. Cyclic AMP-independent effects of cholera toxin on B cell activation. II. Binding of ganglioside G M1 induces B cell activation. J. Immunol. 148: 1999& 2005.
50. Freer, J. H.,, and T. H. Birkbeck. 1982. Possible conformation of delta-lysin, a membrane-damaging peptide of Staphylococcus aureus. J. Theor. Biol. 94: 535 540.
51. Fukuta, S.,, E. M. Twiddy,, J. L. Magnani,, V. Ginsburg,, and R. K. Holmes. 1988. Comparison of the carbohydrate binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTH-1, LT-1a, and LT-1b. Infect. Immun. 56: 1748 1753.
52. Gaginella, T. S., 1990. Eicosanoid-mediated intestinal secretion, p. 15& 30. In E. Lebenthal, and M. E. Duffey (ed.), Textbook of Secretory Diarrhea. Raven Press, New York.
53. Galen, J. E.,, J. M. Ketley,, A. Fasano,, S. H. Richardson,, S. S. Wasserman,, and J. B. Kaper. 1992. Role of Vibrio cholerae neuraminidase in the function of cholera toxin. Infect. Immun. 60: 406 415.
54. Gallut, J., 1974. Bacteriology, p. 17 40. In D. Barua, and W. Burrows (ed.), Cholera. The W. B. Saunders Co., Philadelphia.
55. Gennaro, M. L.,, P. J. Greenaway,, and D. A. Broadbent. 1982. The expression of biologically active cholera toxin in Escherichia coli. Nucleic Acids Res. 10: 4883 4890.
56. Gill, D. M. 1976. The arrangement of subunits in cholera toxin. Biochemistry 15: 1242 1248.
57. Gill, D. M.,, and C. A. King. 1975. The mechanism of action of cholera toxin in pigeon erythrocyte lysates. J. Biol. Chem. 250: 6424 6432.
58. Gill, D. M.,, and R. S. Rappaport. 1979. Origin of the enzymatically active Al fragment of cholera toxin. J. Infect. Dis. 139: 674 680.
59. Goldberg, I.,, and J. J. Mekalanos. 1986. Effect of a recA mutation on cholera toxin gene amplification and deletion events. J. Bacteriol. 165: 723 731.
60. Gonzalez-Marischal, L.,, R. G. Contreras,, J. J. Bolívar,, A. Ponce,, B. Chávez de Ramirez,, and M. Cereijido. 1990. Role of calcium in tight junction formation between epithelial cells. Am. J. Physiol. 259: C978 C986.
61. Griffiths, S. L.,, R. A. Finkelstein,, and D. R. Critchley. 1986. Characterization of the receptor for cholera toxin and Escherichia coli heat-labile toxin in rabbit intestinal brash borders. Biochem. J. 238: 313 322.
62. Gumbiner, B. 1987. Structure, biochemistry, and assembly of epithelial tight junctions. Am. J. Physiol. 253: C749 C758.
63. Haksar, A.,, D. V. Maudsley,, and F. G. Peron. 1974. Neuraminidase treatment of adrenal cells increases their response to cholera enterotoxin. Nature (London) 251: 514 515.
64. Hardy, S. J.,, J. Holmgren,, S. Johansson,, J. Sanchez,, and T. R. Hirst. 1988. Coordinated assembly of multisubunit proteins: oligomerization of bacterial enterotoxins in vivo and in vitro. Proc. Natl. Acad. Sci. USA 85: 7109 7113.
65. Häse, C. C.,, and R. A. Finkelstein. 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 3317.
66. Hecht, G.,, C. Pothoulakis,, J. T. LaMont,, and J. L. Madara. 1988. Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of the cultured human. J. Clin. Invest. 82: 1516 1524.
67. Hepler, J. R.,, and A. G. Gilman. 1992. G proteins. Trends Biochem. Sci. 17: 383 387.
68. Hirst, T. R., 1991. Assembly and secretion of oligomeric toxins by Gram-negative bacteria, p. 75 100. In J. E. Alouf, and J. H. Freer (ed.), Sourcebook of Bacterial Protein Toxins. Academic Press, Ltd., London.
69. Hirst, T. R.,, J. Sanchez,, J. B. Kaper,, S. J. Hardy,, and J. Holmgren. 1984. Mechanism of toxin secretion by Vibrio cholerae investigated in strains harboring plasmids that encode heat-labile enterotoxins of Escherichia coli. Proc. Natl. Acad. Sci. USA 81: 7752 7756.
70. Holmes, R. K.,, and E. M. Twiddy. 1983. Characterization of monoclonal antibodies that react with unique and cross-reacting determinants of cholera enterotoxin and its subunits. Infec. Immun. 42: 914 923.
71. Holmgren, J., 1992. Pathogenesis, p. 199& 208. In D. Barua, and W. B. Greenough ID. (ed.), Cholera. Plenum Medical Book Co., New York..
72. Holmgren, J.,, I. Lonnroth,, J. Mansson,, and L. Svennerholm. 1975. Interaction of cholera toxin and membrane G M1 ganglioside of small intestine. Proc. Natl. Acad. Sci. USA 72: 2520 2524.
73. Holmgren, J.,, I. Lonnroth,, and L. Svennerholm. 1973. Tissue receptor for cholera exotoxin: postulated structure studies with G M1 ganglioside and related glycoproteins. Infec. Immun. 8: 208 214.
74. Honda, T.,, and R. A. Finkelstein. 1979. Purification and characterization of a hemolysin produced by Vibrio cholerae biotype El Tor: another toxic substance produced by cholera vibrios. Infect. Immun. 26: 1020 1027.
75. Honda, T.,, M. Nishibuchi,, T. Miwatani,, and J. B. Kaper. 1986. Demonstration of a plasmid-borne gene encoding a thermostable direct hemolysin in Vibrio cholerae non-O1 strains. Appl. Environ. Microbiol. 52: 1218 1220.
76. Ichinose, Y.,, K. Yamamoto,, N. Nakasone,, M. J. Tanabe,, T. Takeda,, T. Miwatani,, and M. Iwanaga. 1987. Enterotoxicity of El Tor-like hemolysin of non-O1 Vibrio cholerae. Infect. Immun. 55: 1090 1093.
77. Janicot, M.,, and B. Desbuquois. 1987. Fate of injected l25I-labeled cholera toxin taken up by rat liver in vivo. Generation of the active A1 peptide in the endosomal compartment. Eur. J. Biochem. 161: 433 442.
78. Janicot, M.,, F. Fouque,, and B. Desbuquois. 1991. Activation of rat liver adenylate cyclase by cholera toxin requires toxin internalization and processing in endosome. J. Biol. Chem. 266: 12858 12865.
79. Jobling, M. G.,, and R. K. Holmes. 1991. Analysis of structure and function of the B subunit of cholera toxin by the use of site-directed mutagenesis. Mol. Microbiol. 5: 1755 1767.
80. Johnson, J. A.,, J. G. Morris, Jr.,, and J. B. Kaper. 1993. Gene encoding zonula occludens toxin ( zot) does not occur independently from cholera enterotoxin genes ( ctx) in Vibrio cholerae. J. Clin. Microbiol. 31: 732 733.
81. Kabir, S.,, N. Ahmad,, and S. Ali. 1984. Neuraminidase production by Vibrio cholerae O1 and other diarrheagenic bacteria. Infect. Immun. 44: 747 749.
82. Kahn, R. A.,, and A. G. Gilman. 1984. ADP-ribosylation of G s promotes dissociation of its a and b subunits. J. Biol. Chem. 259: 6235 6240.
83. Kandel, G.,, A. Donohue-Rolfe,, M. Donowitz,, and G. T. Keusch. 1989. Pathogenesis of shigella diarrhea. XVI. Selective targetting of Shiga toxin to villus cells of rabbit jejunum explains the effect of the toxin on intestinal electrolyte transport. J. Clin. Invest. 84: 1509 1517.
84. Kaper, J. B.,, and M. M. Levine. 1981. Cloned cholera enterotoxin genes in study and prevention of cholera. Lancet ii: 1162 1163.
85. Kaper, J. B.,, H. Lockman,, M. M. Baldini,, and M. M. Levine. 1984. A recombinant live oral choiera vaccine. Bio/Technology 2: 345 349.
86. Kaper, J. B.,, H. Lockman,, M. M. Baldini,, and M. M. Levine. 1984. Recombinant nontoxinogenic Vibrio cholerae strains as attenuated cholera vaccine candidates. Nature (London) 308: 655 658.
87. Kaper, J. B.,, H. L. T. Mobley,, J. M. Mi-chalski,, D. A. Herrington,, and M. M. Levine,. 1988. Recent advances in developing a safe and effective live oral attenuated Vibrio cholerae vaccine, p. 161 167. In N. Ohtomo, and R. B. Sack (ed.), Advances in Research on Cholera and Related Diarrheas, vol. 6. KTK Scientific Publishers, Tokyo.
88. Kaper, J. B.,, S. L. Moseley,, and S. Falkow. 1981. Molecular characterization of environmental and nontoxigenic strains of Vibrio cholerae. Infect. Immun. 32: 661 667.
89. Kapral, F. A.,, A. D. O’Brien,, P. D. Ruff,, and W. J. Drugan, Jr. 1976. Inhibition of water absorption in the intestine by Staphylococcus aureus delta-toxin. Infect. Immun. 13: 140 145.
90. Karasawa, T.,, T. Minara,, H. Kurazono,, G. B. Nair,, S. Garg,, T. Ramamurthy,, and Y. Takeda. 1993. Distribution of the zot (zonula occludens toxin) gene among strains of Vibrio cholerae O1 and non-O1. FEMS Microbiol. Lett. 106: 143 146.
91. Kazemi, M.,, and R. A. Finkelstein. 1990. Study of epitopes of cholera enterotoxin-related enterotoxins by checkerboard immunoblotting. Infect. Immun. 58: 2352 2360.
92. Kazemi, M.,, and R. A. Finkelstein. 1991. Mapping epitopic regions of cholera toxin B-subunit protein. Mol. Immunol. 28: 865 876.
93. Ketley, J. M.,, J. Michalski,, J. Galen,, M. M. Levine,, and J. B. Kaper. 1993. Construction of genetically-marked Vibrio cholerae Ol vaccine strains. FEMS Microbiol. Lett. 111: 15 22.
94. Kimberg, D. K.,, M. Field,, J. Johnson,, E. Henderson,, and E. Gershon. 1971. Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J. Clin. Invest. 50: 1218 1230.
95. King, C. C.,, and W. E. van Heyningen. 1973. Deactivation of cholera toxin by a sialidase-resistant monosialosylganglioside. J. Infect. Dis. 127: 639 647.
96. Koch, R. 1884. An address on cholera and its bacillus. Br. Med. J. 2: 403 407.
97. Koonin, E. V. 1992. The second cholera toxin, Zot, and its plasmid-encoded and phage-encoded homologues constitute a group of putative ATP-ases with an altered purine NTP-binding motif. FEBS Lett. 312: 3 6.
98. Krasilnikov, O. V.,, J. N. Muratkhodjaev,, A. E. Voronov,, and Y. V. Yezepchuk. 1991. The ionic channels formed by cholera toxin planar bi-layer lipid membranes are entirely attributable to its B-subunit. Biochim. Biophys. Acta 1067: 166 170.
99. Krasilnikov, O. V.,, J. N. Muratkhodjaev,, and A. O. Zitzer. 1992. The mode of action of Vibrio cholerae cytolysin. The influences on both erythrocytes and planar lipid -bilayers. Biochim. Biophys. Acta 1111: 7 16.
100. Krause, M.,, C. Roudier,, J. Fierer,, J. Harwood,, and D. Guiney. 1991. Molecular analysis of the virulence locus of the Salmonella dublin plasmid pSDL2. Mol. Microbiol. 5: 307 316.
101. Lencer, W. L.,, J. B. de Almeida,, S. Moe,, J. L. Stow,, D. A. Ausiello,, and J. L. Madara. 1993. Entry of cholera toxin into polarized human epithelial cells: identification of an early brefeldin-A sensitive event required for A 1 peptide generation. J. Clin. Invest. 92: 2941 2951.
102. Lencer, W. L.,, C. Delp,, M. R. Neutra,, and J. L. Madara. 1992. Mechanism of cholera toxin action on a polarized human intestinal epithelial cell line: role of vesicular traffic. J. Cell Biol. 117: 1197 1209.
103. Levine, M. M., 1980. Immunity to cholera as evaluated in volunteers, p. 195 203. In O. Ouchterlony, and J. Holmgren (ed.), Cholera and Related Diarrheas. Karger, Basel..
104. Levine, M. M.,, J. B. Kaper,, R. E. Black,, and M. L. Clements. 1983. New knowledge on pathogenesis of bacterial enteric infections as applied to vaccine development. Microbiol. Rev. 47: 510 550.
105. Levine, M. M.,, J. B. Kaper,, D. Herrington,, J. Ketley,, G. Losonsky,, C. O. Tacket,, B. Tall,, and S. Cryz. 1988. Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. Lancet ii: 467 470.
106. Levine, M. M.,, J. B. Kaper,, D. Herrington,, G. Losonsky,, J. G. Morris,, M. L. Clements,, R. E. Black,, B. TaU,, and R. Hall. 1988. Volunteer studies of deletion mutants of Vibrio cholerae O1 prepared by recombinant techniques. Infect. Immun. 56: 161 167.
107. Levine, M. M.,, D. R. Nalin,, D. L. Hoover,, E. J. Bergquist,, R. B. Hornick,, and C. R. Young. 1979. Immunity to enterotoxigenic Escherichia coli. Infect. Immun. 23: 729 736.
108. Liang, X.,, M. E. Lamm,, and J. G. Nedrud. 1988. Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus. J. Immunol. 141: 1495 1501.
109. Lind, C. D.,, R. H. Davis,, R. L. Guerrant,, J. B. Kaper,, and J. R. Mathias. 1991. Effects of Vibrio cholerae recombinant strains on rabbit ileum in vivo. Enterotoxin production and myoelectric activity. Gastroenterology 101: 319 324.
110. Lindholm, L.,, J. Holmgren,, M. Wikstrom,, U. Karlsson,, K. Andersson,, and N. Lycke. 1983. Monoclonal antibodies to cholera toxin with special reference to cross-reactions with Escherichia coli heat-labile enterotoxin. Infect. Immun. 40: 570 576.
111. Lockman, H.,, and J. B. Kaper. 1983. Nucleotide sequence analysis of the A2 and B subunits of Vibrio cholerae enterotoxin. J. Biol. Chem. 258: 13722 13726.
112. Lockman, H. A.,, J. E. Galen,, and J. B. Kaper. 1984. Vibrio cholerae enterotoxin genes: nucleotide sequence analysis of DNA encoding ADP-ribosyltransferase. J. Bacteriol. 159: 1086 1089.
113. London, E. 1992. How bacterial protein toxins enter cells: the role of partial unfolding in membrane translocation. Mol. Microbiol. 6: 3277 3282.
114. Ludwig, D. S.,, R. K. Holmes,, and G. K. Schoolnik. 1985. Chemical and immunochemical studies on the receptor binding domain of cholera toxin B subunit. J. Biol. Chem. 260: 12528 12534.
115. Lundgren, O., 1988. Factors controlling absorption and secretion in the small intestine, p. 97 112. In W. Donachie,, E. Griffiths,, and J. Stephen (ed.), Bacterial Infections of Respiratory and Gastrointestinal Mucosae. IRL Press, Oxford.
116. Lycke, N.,, and J. Holmgren. 1986. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology 59: 301 308.
117. Lycke, N.,, U. Karlsson,, A. Sjölander,, and K.-E. Magnusson. 1991. The adjuvant action of cholera toxin is associated with an increased intestinal permeability for luminal antigens. Scand. J. Immunol. 33: 691 698.
118. Lycke, N.,, and W. Straber. 1989. Cholera toxin promotes B cell isotype differentiation. J. Immunol. 142: 3781 3787.
119. Lycke, N.,, T. Tsuji,, and J. Holmgren. 1992. The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile enterotoxins is linked to their ADP-ribosyltransferase activity. Eur. J. Immunol. 22: 2277 2281.
120. Lycke, N. Y.,, and A.-M. Svennerholm,. 1990. Presentation of immunogens at the gut and other mucosal surfaces, p. 207 227. In G. C. Woodrow, and M. M. Levine (ed.), New Generation Vaccines. Marcel Dekker, Inc., New York.
121. Madara, J. L. 1989. Loosening tight junctions—lessons from the intestine. J. Clin. Invest. 83: 1089 1094.
122. Madara, J. L., 1990. Contributions of the paracellular pathway to secretion, absorption, and barrier function in the epithelium of the small intestine, p. 125 138. In E. Lebenthal, and M. Duffey (ed.), Textbook of Secretory Diarrhea. Raven Press, Ltd., New York.
123. Mathan, V. I.,, and M. Mathan. Unpublished data.
124. Mathias, J. R.,, G. M. Carlson,, A. J. DiMarino,, G. Bertiger,, H. E. Morton,, and S. Cohen. 1976. Intestinal myoelectric activity in response to live Vibrio cholerae and cholera enterotoxin. J. Clin. Invest. 58: 91 96.
125. McCardell, B.,, J. M. Madden,, and D. B. Shah. 1985. Isolation and characterization of a cytolysin produced by Vibrio cholerae serogroup non-O1. Can. J. Microbiol. 31: 711 720.
126. Mekalanos, J. J. 1983. Duplication and amplification of toxin genes in Vibrio cholerae. Cell 35: 253 263.
127. Mekalanos, J. J. 1985. Cholera toxin: genetic analysis, regulation, and role in pathogenesis. Curr. Top. Microbiol. Immunol. 118: 97 118.
128. Mekalanos, J. J.,, D. J. Swartz,, G. D. Pearson,, N. Harford,, F. Groyne,, and M. de Wilde. 1983. Cholera toxin genes: nucleotide sequence, deletiori analysis and vaccine development. Nature (London) 306: 551 557.
129. Michalski, J.,, J. E. Galen,, A. Fasano,, and J. B. Kaper. 1993. CVD110, an attenuated Vibrio cholerae O1 El Tor live oral vaccine strain. Infect. Immun. 61: 4462 4468.
130. Michalski, J. M.,, and J. B. Kaper. Unpublished data.
131. Miller, V. L.,, and J. J. Mekalanos. 1984. Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. Proc. Natl. Acad. Sci. USA 81: 3471 3475.
132. Miller-Podraza, H.,, R. M. Bradley,, and R. H. Fishman. 1982. Biosynthesis and localization of gangliosides in cultured cells. Biochemistry 21: 3260 3265.
133. Moore, R.,, C. Pothoulakis,, J. T. LaMont,, S. Carlson,, and J. Madara. 1990. C. difficile toxin A increases intestinal permeability and induces Cl-secretion. Am. J. Physiol. 259: G165 G172.
134. Moriarty, K. J.,, N. B. Higgs,, M. Woodford,, and L. A. Turnberg. 1989. An investigation of the role of possible neural mechanisms in cholera toxin-induced secretion in rabbit ileal mucosa in vitro. Clin. Sci. 77: 161 166.
135. Morris, J. G., Jr.,, T. Takeda,, B. D. Tall,, G. A. Losonsky,, S. K. Bhattacharya,, B. D. Forrest,, B. A. Kay,, and M. Nishibuchi. 1990. Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans. J. Clin. Invest. 85: 697 705.
136. Moseley, S. L.,, and S. Falkow. 1980. Nucleotide sequence homology between the heat-labile enterotoxin gene of Escherichia coli and Vibrio cholerae. J. Bacteriol. 144: 444 446.
137. Moss, J.,, and M. Vaughan. 1977. Mechanism of activation of choleragen. Evidence for ADP-ribosyltransferase activity with arginine as an acceptor. J. Biol. Chem. 252: 2455 2457.
138. Moss, J.,, and M. Vaughan. 1991. Activation of cholera toxin and Escherichia coli heat-labile enterotoxins by ADP-ribosylation factors, a family of 20-kDa guanine nucleotide-binding proteins. Mol. Microbiol. 5: 2621 2627.
139. Mullin, J. M.,, and T. O’Brien. 1986. Effects of tumor promoters on LLC-pk, renal epithelial tight junctions and transepithelial fluxes. Am. J. Physiol. 251: C597 C602.
140. Mullin, J. M.,, and K. V. Snock. 1990. Effect of tumor necrosis factor on epithelial tight junctions and transepithelial permeability. Cancer Res. 50: 2172 2176.
141. Munoz, E.,, A. M. Zubiaga,, M. Merrow,, N. P. Sauter,, and B. T. Huber. 1990. Cholera toxin discriminates between T helper 1 and T helper 2 cells in T cell receptor mediated activation: role of cAMP in T cell proliferation. J. Exp. Med. 172: 95 103.
142. Muron, S.,, and H. R. B.. Pelham. 1987. A C-terminal signal prevents secretion of luminal ER proteins. Cell 48: 899 907.
143. Nambiar, M. P.,, T. Oda,, C. Chen,, Y. Kuwazuru,, and H. C. Wu. 1993. Involvement of the Golgi region in the intracellular trafficking of cholera toxin. J. Cell. Physiol. 154: 222 228.
144. Nilsson, O.,, J. Cassuto,, P.-A. Larsson,, M. Jodal,, P. Lidberg,, H. Animan,, A. Dahlström,, and O. Lundgren. 1983. 5-Hydroxytryptamine and cholera secretion: a histochemical and physiological study in cats. Gut 24: 542 548.
145. Nishibuchi, M.,, A. Fasano,, R. G. Russell,, and J. B. Kaper. 1992. Enterotoxigenicity of Vibrio parahaemolyticus with and without genes encoding thermostable direct hemolysin. Infect. Immun. 60: 3539 3545.
146. Noguchi, T.,, J. K. Jeon,, O. Arakawa,, H. Sug-ita,, Y. Deguchi,, Y. Shida,, and K. Hashimoto. 1986. Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus. J. Biochem. (Tokyo) 99: 311 314.
147. O’Brien, A. D.,, M. E. Chen,, R. K. Holmes,, J. Kaper,, and M. M. Levine. 1984. Environmental and human isolates of Vibrio cholerae and Vibrio parahaemolyticus produce a Shigella dysenteriae 1 (Shiga)-like cytotoxin. Lancet i: 77 78.
148. O’Brien, A. D.,, and F. A. Kapral. 1976. Increased cyclic adenosine 3' ,5' -monophosphate content in guinea pig ileum after exposure to Staphylococcus aureus delta-toxin. Infect. Immun. 13: 152 162.
149. Ogawa, A.,, J.-I. Kato,, H. Watanabe,, B. G. Nair,, and T. Takeda. 1990. 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. 58: 3325 3329.
150. Olsvik, Ø.,, J. Wahlberg,, B. Petterson,, M. Uhlen,, T. Popovic,, I. K. Wachsmuth,, and P. I. Fields. 1993. Use of automated sequencing of polymerase chain reaction-generated amplicons to identify three types of cholera toxin subunit B in Vibrio cholerae O1 strains. J. Clin. Microbiol. 31: 22 25.
151. Pearson, G. D.,, V. J. DiRita,, M. B. Goldberg,, S. A. Boyko,, S. B. Calder wood,, and J. J. Mekalanos. 1990. New attenuated derivatives of Vibrio cholerae. Res. Microbiol. 141: 893 899.
152. Pearson, G. D.,, and J. J. Mekalanos. 1982. Molecular cloning of Vibrio cholerae enterotoxin genes in Escherichia coli K-12. Proc. Natl. Acad. Sci. USA 79: 2976 2980.
153. Pearson, G. D. N.,, A. Woods,, S. L. Chiang,, and J. J. Mekalanos. 1993. CTX genetic element encodes a site-specific recombination system and an intestinal colonization factor. Proc. Natl. Acad. Sci. USA 90: 3750 3754.
154. Peek, J. A.,, and R. K. Taylor. 1992. Characterization of periplasmic thiol:disulfide interchange protein required for the functional maturation of secreted virulence factors of Vibrio cholerae. Proc. Natl. Acad. Sci. USA 89: 6210 6214.
155. Peterson, J. W.,, K. E. Hejtmancik,, D. E. Markel,, J. P. Craig,, and A. Kurosky. 1979. Antigenic specificity of neutralizing antibody to cholera toxin. Infect. Immun. 24: 774 779.
156. Peterson, J. W.,, and L. G. Ochoa. 1989. Role of prostaglandins and cAMP in the secretory effects of cholera toxin. Science 245: 857 859.
157. Peterson, J. W.,, J. C. Reitmeyer,, C. A. Jackson,, and G. A. S. Ansari. 1991. Protein synthesis is required for cholera toxin-induced stimulation of arachidonic acid metabolism. Biochim. Biophys. Acta 1092: 79 84.
158. Pierce, N. F. 1973. Differential inhibitory effects of cholera toxoids and ganglioside on the enterotoxin of Vibrio cholerae and Escherichia coli. J. Exp. Med. 137: 1009 1023.
159. Rabbani, G. H.,, W. Greenough III,, J. Holmgren,, and I. Lonnroth. 1979. Chlor-promazine reduces fluid-loss in cholera. Lancet i: 410 412.
160. Rabbani, G. H.,, and W. B. Greenough III,. 1992. Pathophysiology and clinical aspects of cholera, p. 209 228. In D. Barua, and W. B. Greenough III (ed.), Cholera. Plenum Medical Book Co., New York.
161. Reitmeyer, J. C.,, and J. W. Peterson. 1990. Stimulatory effects of cholera toxin on arachidonic acid metabolism in Chinese hamster ovary cells. Proc. Soc. Exp. Biol. Med. 193: 181 184.
162. Ribi, H. O.,, D. S. Ludwig,, K. L. Mercer,, G. K. Schoolnik,, and R. D. Kornberg. 1988. Three-dimensional structure of cholera toxin penetrating a lipid membrane. Science 239: 1272 1276.
163. Richardson, K.,, J. Michalski,, and J. B. Kaper. 1986. Hemolysin production and cloning of two hemolysin determinants from classical Vibrio cholerae. Infect. Immun. 54: 415 420.
164. Rodman, D. M.,, and S. Zamudio. 1991. The cystic fibrosis hétérozygote—advantage in surviving cholera? Med. Hypoth. 36: 253 258.
165. Saha, S.,, and S. C. Sanyal. 1988. Cholera toxin gene-positive Vibrio cholerae O1 Ogawa and Inaba strains produce the new cholera toxin. FEMS Microbiol. Lett. 50: 113 116.
166. Saha, S.,, and S. C. Sanyal. 1990. Immunobiological relationships of the enterotoxins produced by cholera toxin gene-positive (CT +) and -negative (CT -) strains of Vibrio cholerae O1. J. Med. Microbiol. 32: 33 37.
167. Sanchez, J.,, S. Johansson,, B. Lowenadler,, A. M. Svennerholm,, and J. Holmgren. 1990. Recombinant cholera toxin B subunit and gene fusion proteins for oral vaccination. Res. Microbiol. 141: 971 979.
168. Sandkvist, M.,, V. Morales,, and M. Bagdasarian. 1993. A protein required for secretion of cholera toxin through the outer membrane of Vibrio cholerae. Gene 123: 81 86.
169. Sanyal, S. C.,, K. Alam,, P. K. B. Neogi,, M. I. Huq,, and K. A. Al-Mahmud. 1983. A new cholera toxin. Lancet i: 1337.
170. Schödel, F,, H. Will,, S. Johansson,, J. Sanchez,, and J. Holmgren. 1991. Synthesis in Vibrio cholerae and secretion of hepatitis B virus antigens fused to Escherichia coli heat-labile enterotoxin subunit B. Gene 99: 255 259.
171. Sixma, T. K.,, S. E. Pronk,, K. H. Kalk,, B. A. M. van Zanten,, A. M. Berghuis,, and W. G. J. Hol. 1992. Lactose binding to heat-labile enterotoxin revealed by X-ray crystallography. Nature (London) 355: 561 564.
172. Sixma, T. K.,, S. E. Pronk,, K. H. Kalk,, E. S. Wartna,, B. A. M. van Zanten,, B. Witholt,, and W. G. J. Hol. 1991. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature (London) 351: 371 377.
173. Sjöqvist, A.,, J. Cassuto,, M. Jodal,, and O. Lundgren. 1992. Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion. Acta Physiol. Scand. 145: 229 237.
174. Smith, H. W.,, and M. A. Linggood. 1971. Observations on the pathogenic properties of the K88, Hly and Ent plasmids of Escherichia coli with particular reference to porcine diarrhoea. J. Med. Microbiol. 4: 467 485.
175. Spengler, B. D. 1992. Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol. Rev. 56: 622 647.
176. Speelman, P.,, G. H. Rabbani,, K. Bukhave,, and J. Rask-Madsen. 1985. Increased jejunal prostaglandin E 2 concentrations in patients with acute cholera. Gut 26: 188 193.
177. Spira, W. M.,, D. A. Sack,, P. J. Fedorka-Cray,, S. Sanyal,, J. Madden,, and B. McCardell,. 1986. Description of a possible new extracellular virulence factor in nontoxigenic Vibrio cholerae O1, p. 263 270. In S. Kuwahara, and N. F. Pierce (ed.), Advances in Research in Cholera and Related Diarrheas, vol. 3. KTK Scientific Publishers, Tokyo.
178. Staerk, J.,, H. J. Ronneberger,, and H. Wiegandt. 1974. Neuraminidase, a virulence factor in Vibrio cholerae infection? Behring Inst. Mitt. 55: 145 146.
179. Svennerholm, A.-M., 1980. The nature of protective immunity in cholera, p. 171 184. In O. Ouchterlony, and J. Holmgren (ed.), Cholera and Related Diarrheas. 43rd Nobel Symposium, Stockholm, 1978. S. Karger, Basel.
180. Svennerholm, A. M.,, G. J. Stromberg,, and J. Holmgren. 1983. Purification of Vibrio cholerae soluble hemagglutinin and development of enzyme-linked immunosorbent assays for antigen and antibody quantitations. Infect. Immun. 41: 237 243.
181. Tacket, C. O.,, G. Losonsky,, J. P. Nataro,, S. J. Cryz,, R. Edelman,, A. Fasano,, J. Michalski,, J. B. Kaper,, and M. M. Levine. Safety, immunogenicity, and transmissibility of live oral cholera vaccine candidate CVD110, a δ ctxA δ zot δ ace derivative of El Tor Ogawa Vibrio cholerae. J. Infect. Dis., in press.
182. Takeda, T.,, Y. Peina,, A. Ogawa,, S. Dohi,, H. Abe,, G. B. Nair,, and S. C. Pal. 1991. Detection of heat-stable enterotoxin in a cholera toxin gene-positive strain of Vibrio cholerae O1. FEMS Microbiol. Lett. 80: 23 28.
183. Tamplin, M. L.,, M. K. Ahmed,, R. Jalali,, and R. R. Colwell. 1989. Variation in epitopes of the B subunit of El Tor and classical biotype Vibrio cholerae O1 cholera toxin. J. Gen. Microbiol. 135: 1195 1200.
184. Tamplin, M. L.,, R. R. Colwell,, S. Hall,, K. Kogure,, and G. R. Strichartz. 1987. Sodium-channel inhibitors produced by enteropathogenic Vibrio cholerae and Aeromonas hydrophila. Lancet i: 975.
185. Taylor, S. S.,, J. Bubis,, J. Toner Webb,, L. D. Saraswat,, E. A. First,, J. A. Buechler,, D. R. Knighton,, and J. Sowadski. 1988. CAMP-dependent protein kinase: prototype for a family of enzymes. FASEB J. 2: 2677 2685.
186. Terai, A.,, K. Baba,, H. Shirai,, O. Yoshida,, Y. Takeda,, and M. Nishibuchi. 1991. Evidence for insertion-sequence-mediated spread of the thermostable direct hemolysin gene among Vibrio species. J. Bacteriol. 173: 5036 5046.
187. Tornasi, M., and C. Montecucco. 1981. Lipid insertion of cholera toxin after binding to GM 1-containing liposomes. J. Biol. Chem. 256: 11177 11181.
188. Trucksis, M.,, J. E. Galen,, J. Michalski,, A. Fasano,, and J. B. Kaper. 1993. Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette. Proc. Natl. Acad. Sci. USA 90: 5267 5271.
189. Trucksis, M.,, and J. B. Kaper. Unpublished data.
190. Tucker, K. D.,, P. E. Carrig,, and T. D. Wilkins. 1990. Toxin A of Clostridium difficile is a potent cytotoxin. J. Clin. Microbiol. 28: 869 871.
191. van Heyningen, S. 1991. The ring on a finger. Nature (London) 351: 351.
192. van Heyningen, W. E.,, and J. R. Seal. 1983. Cholera—The American Scientific Experience, 1947-1980. Westview Press, Boulder, Colo..
193. Wanke, C. A.,, and R. L. Guerrant. 1987. Small-bowel colonization alone is a cause of diarrhea. Infect. Immun. 55: 1924 1926.
194. Westbrook, E. Personal communication.
195. Wisnieski, B. J.,, and J. S. Bramhall. 1981. Photolabelling of cholera toxin subunits during membrane penetration. Nature (London) 289: 319 321.
196. Yamamoto, K.,, Y. Ichinose,, N. Nakasone,, M. Tanabe,, M. Nagahama,, J. Sakurai,, and M. Iwanaga. 1986. Identity of hemolysins produced by Vibrio cholerae non-O1 and V. cholerae O1, biotype El Tor. Infect. Immun. 51: 927 931.
197. Yamamoto, K.,, Y. Ichinose,, H. Shinagawa,, K. Makino,, A. Nakata,, M. Iwanaga,, T. Honda,, and T. Miwatani. 1990. Two-step processing for activation of the cytolysin/hemolysin of Vibrio cholerae O1 biotype El Tor: nucleotide sequence of the structural gene ( hlyA) and characterization of the processed products. Infect. Immun. 58: 4106 4116.
198. Yamamoto, K.,, A. C. Wright,, J. B. Kaper,, and J. G. Morris. 1990. The cytolysin gene of Vibrio vulnificus: sequence and relationship to the Vibrio cholerae El Tor hemolysin gene. Infect. Immun. 58: 2706 2709.
199. Yamamoto, T.,, T. Gojobori,, and T. Yokota. 1987. Evolutionary origin of pathogenic determinants in enterotoxigenic Escherichia coli and Vibrio cholerae O1.7. Bacteriol. 169: 1352 1357.
200. Yamamoto, T.,, T. Tamura,, and T. Yokota. 1984. Primary structure of heat-labile enterotoxin produced by Escherichia coli pathogenic for humans. J. Biol. Chem. 259: 5037 5044.
201. Yamamoto, T.,, and T. Yokota. 1983. Sequence of heat-labile enterotoxin of Escherichia coli pathogenic for humans. J. Bacteriol. 155: 728 733.
202. Yu, J.,, H. Webb,, and T. R. Hirst. 1992. A homologue of the Escherichia coli DsbA protein involved in disulphide bond formation is required for enterotoxin biogenesis in Vibrio cholerae. Mol. Microbiol. 6: 1949 1958.

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