Nature 292, 413 - 417 (30 July 1981); doi:10.1038/292413a0

Actions of cholera toxin and the prevention and treatment of cholera

Jan Holmgren

Institute of Medical Microbiology, University of Göteborg, S-413 46 Göteborg, Sweden

The drastic intestinal secretion of fluid and electrolytes that is characteristic of cholera is the result of reasonably well understood cellular and biochemical actions of the toxin secreted by Vibrio cholerae. Based on this understanding it is possible to devise new techniques for the treatment and prophylaxis of cholera to complement those based on fluid replacement therapy and sanitation.

References

1.	Ouchterlony, Ö. & Holmgren, J. (eds) Cholera and Related Diarrhoeas: 43rd Nobel Symp., Stockholm 1978 (Karger, Basel, 1980).
2.	De, S. N. Nature 183, 1533−1534 (1959). | PubMed | ISI | ChemPort |
3.	Dutta, N. K., Panse, M. V. & Kulkarni, D. R. J. Bact. 78, 594−595 (1959). | PubMed | ISI | ChemPort |
4.	Finkelstein, R. A. & LoSpalluto, J. J. J. exp. Med. 130, 185−202 (1969). | Article | PubMed | ISI | ChemPort |
5.	Richardson, S. H., Evans, D. G. & Feeley, J. C. Infect. Immunity 1, 546−553 (1970). | ChemPort |
6.	Field, M., Fromm, D., Wallace, C. K. & Greenough, W. B. J. clin. Invest. 48, 24a (1969).
7.	Schafer, D. E., Lust, W. D., Sircar, B. & Goldberg, N. D. Proc. natn. Acad. Sci. U.S.A. 67, 851−856 (1970). | ChemPort |
8.	Sharp, G. W. G. & Hynie, S. Nature 229, 266−269 (1971). | PubMed | ISI | ChemPort |
9.	Field, M., Fromm, D., Al-Awqati, Q. & Greenough, W. B. J. clin. Invest. 51, 795−804 (1972).
10.	Greenough, W. B., Pierce, N. F. & Vaughan, M. J. infect. Dis. 121, S111−S114 (1970). | ISI |
11.	Lönnroth, I. & Holmgren, J. J. gen. Microbiol. 76, 417−427 (1973). | PubMed |
12.	Cuatrecasas, P., Parikh, I. & Hollenberg, M. D. Biochemistry 12, 4253−4264 (1973). | PubMed | ISI | ChemPort |
13.	Holmgren, J. Proc. 9th Joint US-Japan Cholera Conf., Grand Canyon 1973, 196−213 (Dept of State Publ. 8762, Washington, 1973).
14.	Heyningen, S. van. Science 183, 656−657 (1974). | PubMed |
15.	Holmgren, J., Lindholm, L. & Lönnroth, I. J. exp. Med. 139, 801−819 (1974). | Article | PubMed | ISI | ChemPort |
16.	Finkelstein, R. A., Boesman, M., Neoh, S. H., LaRue, N. K. & Delaney, R. J. Immun. 113, 175−180 (1974).
17.	Gill, D. M. & King, C. A. J. biol Chem. 250, 424−432 (1975).
18.	Heyningen, S. van. & King, C. A. Biochem. J. 146, 269−271 (1975). | PubMed |
19.	Flores, J. & Sharp, S. W. G. J. clin. Invest. 56, 1345−1349 (1975). | PubMed | ISI | ChemPort |
20.	Mekelanos, J. J., Collier, R. J. & Romig, W. R. J. biol. Chem. 254, 5855−5861 (1979). | PubMed | ISI | ChemPort |
21.	Cuatrecasas, P. Biochemistry 12, 3547−3558 (1973). | PubMed | ISI | ChemPort |
22.	Holmgren, J., Lönnroth, I., Månsson, J. E. & Svennerholm, L. Proc. natn. Acad. Sci. U.S.A. 72, 2520−2524 (1975). | ChemPort |
23.	Fishman, P. H. & Atikkan, E. E. J. biol. Chem. 254, 4342−4344 (1979). | PubMed | ISI | ChemPort |
24.	Heyningen, W. E. van., Carpenter, C. C. J., Pierce, N. F. & Greenough, W. B. J. infect. Dis. 124, 415−418 (1971). | PubMed |
25.	Holmgren, J., Lönnroth, I. & Svennerholm, L. Infect. Immunity 8, 208−214 (1973). | ISI | ChemPort |
26.	King, C. A. & Heyningen, W. E. van. J. infect. Dis. 127, 639−647 (1973). | PubMed | ISI | ChemPort |
27.	Hansson, H.-A., Holmgren, J. & Svennerholm, L. Proc. natn. Acad. Sci. U.S.A. 74, 3782−3786 (1977). | ChemPort |
28.	Fishman, P. H. & Atikkan, E. E. J. biol. Chem. 254, 4342−4344 (1979). | PubMed | ISI | ChemPort |
29.	Holmgren, J. & Lönnroth, I. J. gen. Microbiol. 86, 49−65 (1975). | PubMed | ISI | ChemPort |
30.	Sattler, J., Schwarzmann, G., Staerk, J., Ziegler, W. & Wiegandt, H. Hoppe-Seyler's Z. physiol. Chem. 358, 159−163 (1977). | ChemPort |
31.	Holmgren, J., Månsson, J.-E. & Svennerholm, L. Med. Biol. 52, 229−233 (1974). | PubMed | ISI | ChemPort |
32.	Fishman, P. H., Moss, J. & Osborne, J. C. Biochemistry 17, 711−716 (1978). | PubMed | ISI | ChemPort |
33.	Cuatrecasas, P. Biochemistry 12, 3558−3566 (1973). | PubMed | ISI | ChemPort |
34.	Fishman, P. H., Pacuszka, T., Holm, B. & Moss, J. J. biol. Chem. 255, 7657−7664 (1980). | PubMed | ISI | ChemPort |
35.	Moss, J., Fishman, P. H., Manganiello, V. O., Vaughan, M. & Brady, R. O. Proc. natn. Acad. Sci. U.S.A. 73, 1034−1037 (1976). | ChemPort |
36.	Mullin, B. R. et al. Proc. natn. Acad. Sci. U.S.A. 73, 1679−1683 (1976). | ChemPort |
37.	Holmgren, J. & Lönnroth, I. J. infect. Dis. 133, 564−574 (1976). | PubMed |
38.	Craig, S. W. & Cuatrecasas, P. Proc. natn. Acad. Sci. U.S.A. 72, 3844−3848 (1975). | ChemPort |
39.	Revesz, T. & Greaves, M. Nature 257, 103−106 (1975). | PubMed | ISI | ChemPort |
40.	Sedlacek, H. H., Staerk, J., Seiler, F. R., Ziegler, W. & Wiegand, H. FEBS Lett. 61, 272−276 (1976). | Article | PubMed | ISI | ChemPort |
41.	Bennet, V., O'Keefe, E. & Cuatrecasas, P. Proc. natn. Acad. Sci. U.S.A. 72, 33−37 (1975).
42.	Fishman, P. H. in Secretory Diarrhea (eds Field, M., Fordtran, J. S., & Schultz S. G.) 85−106 (American Physiological Society, Maryland, 1980). | ChemPort |
43.	Moss, J., Richards, R. L., Alving, C. R. & Fishman, P. H. J. biol Chem. 252, 797−798 (1977). | PubMed | ISI | ChemPort |
44.	Tosteson, M. T. & Tosteson, D. C. Nature 275, 142−144 (1978). | PubMed | ISI | ChemPort |
45.	Holmgren, J. & Lönnroth, I. in Cholera and Related Diarrhoeas: 43rd Nobel Symp., Stockholm 1978, 88−103 (Karger, Basel, 1980).
46.	Manuelidis, L. & Manuelidis, E. E. J. Neurocytol. 5, 575−589 (1976). | PubMed | ISI | ChemPort |
47.	Pappenheimer, A. M.Jr, A. Rev. Biochem. 46, 69−94 (1977). | Article | ISI | ChemPort |
48.	Sandvig, K. & Olsnes, S. J. Cell Biol. 87, 828−832 (1980). | Article | PubMed | ISI | ChemPort |
49.	Draper, R. K. & Simon, M. I. J. Cell Biol. 87, 849−854 (1980). | Article | PubMed | ISI | ChemPort |
50.	Gill, D. M. J. infect. Dis. 133, S55−S63 (1976). | ISI |
51.	Moss, J., Manganiello, V. C. & Vaughan, M. Proc. natn. Acad. Sci. U.S. A. 73, 4424−4427 (1976). | ChemPort |
52.	Cassel, D. & Pfeuffer, T. Proc. natn. Acad. Sci. U.S.A. 75, 2669−2673 (1978). | ChemPort |
53.	Gill, D. M. & Mehren, R. Proc. natn. Acad. Sci. U.S.A. 75, 3050−3054 (1978). | ChemPort |
54.	Cassel, D. & Selinger, Z. Proc. natn. Acad. Sci. U.S.A. 74, 3307−3311 (1977). | ChemPort |
55.	Lad, P. M., Nielsen, T. B., Preston, N. S. & Rodbell, M. J. biol. Chem. 255, 988−995 (1980). | PubMed | ISI | ChemPort |
56.	Cash, R. A. et al. J. infect. Dis. 130, 325−333 (1974). | PubMed | ISI | ChemPort |
57.	Feeley, J. C. & Gangarosa, E. J. in Cholera and Related Diarrhoeas: 43rd Nobel Symp. Stockholm 1978, 204−210 (Karger, Basel, 1980).
58.	Svennerholm, A.-M. & Holmgren, J. Infect. Immunity 13, 735−740 (1976). | ISI | ChemPort |
59.	Peterson, J. W. Infect. Immunity 26, 528−533 (1979). | ISI | ChemPort |
60.	Holmgren, J. et al. Nature 269, 602−604 (1977). | PubMed | ISI | ChemPort |
61.	Pierce, N. F. J. exp. Med. 148, 195−206 (1978). | Article | PubMed | ISI | ChemPort |
62.	Ohtomo, N., Muraoka, T. & Tashiro, A. Proc. 10th Joint US−Japan Cholera Conf., Kyoto 1974, 115−118 (Tokyo, 1974).
63.	Svennerholm, A.-M. in Cholera and Related Diarrhoeas: 43rd Nobel Symp., Stockholm 1978, 171−184 (Karger, Basel, 1980).
64.	Peterson, J. W., Hejtmancik, K. E., Markel, D. E., Craig, J. P. & Kurosky, A. Infect. Immunity 24, 774−779 (1979). | ISI | ChemPort |
65.	Svennerholm, A.-M., Sack, D. A., Bardhan, P. K., Jertborn, M. & Holmgren, J. in Proc. 16th US−Japan Cholera Conf. Gifu, 1980 (Osaka University Press, in the press).
66.	Sack, D. A., Islam, A., Holmgren, J. & Svennerholm, A.-M. in Proc. 15th Joint US−Japan Cholera Conf. Bethesda, 1979, 423−439 (NIH Publ. 80-2003, 1980).
67.	Svennerholm, A.-M., Jertborn, M., Gothefors, L., Sack, D. A. & Holmgren, J. (in preparation).
68.	Tayot, J.-L., Holmgren, J., Svennerholm, L., Lindblad, M. & Tardy, J. Eur. J. Biochem. 113, 249−258 (1981). | PubMed | ISI | ChemPort |
69.	Honda, T. & Finkelstein, R. A. Proc. natn. Acad. Sci. U.S.A. 76, 2052−2056 (1979). | ChemPort |
70.	Levine, M. in Nobel Conf. 3 (eds Holme, T., Holmgren, J., Merson, M. & Möllby, R.) (Elsevier, Amsterdam, in the press).
71.	Stoll, B. J. et al. Lancet ii, 888−891 (1980).
72.	Pierce, N. F. J. exp. Med. 137, 1009−1023 (1973). | Article | PubMed | ISI | ChemPort |
73.	Holmgren, J. Infect. Immunity 8, 851−859 (1973). | ISI | ChemPort |
74.	Hirschhorn, N. J. et al. New Engl. J. med. 279, 176−184 (1968). | PubMed | ISI | ChemPort |
75.	Nalin, D. R., Cash, R. A., Islam, R., Molla, M. & Phillips, R. A. Lancet ii, 370−372 (1968). | Article |
76.	Pierce, N. F. et al. Ann. intern. Med. 70, 1173−1183 (1969). | PubMed | ISI | ChemPort |
77.	Schultz, S. G. & Curran, P. F. Curr. Topics Membrane Transport 5, 225−281 (1974). | ChemPort |
78.	Greenough, W. B. III & Hendrix, T. R. in Cholera and Related Diarrhoeas: 43rd Nobel Symp., Stockholm 1978, 234−244 (Karger, Basel, 1980).
79.	Holmgren, J., Lange, S. & Lönnroth, I. Gastroenterology 75, 1103−1108 (1978). | PubMed | ISI | ChemPort |
80.	Lönnroth, I., Lange, S. & Holmgren, J. in Phenothiazines and Structurally Related Drugs: Basic and Clinical Studies (eds Usdin, E., Eckert, H. & Forrest, S. J. J.) 303−306 (Elsevier, New York, 1980).
81.	Turjman, N., Gotterer, G. S. & Hendrix, T. R. J. clin. Invest. 61, 1155−1160 (1978). | PubMed | ISI | ChemPort |
82.	Finch, A. D. & Katz, R. L. Nature 238, 273−274 (1972). | PubMed |
83.	Jacoby, H. I. & Marshall, C. H. Nature 235, 163−165 (1972). | PubMed | ISI | ChemPort |
84.	Carpenter, C. C. J., Curlin, G. T. & Greenough, W. B., J. infect. Dis. 120, 332−338 (1969). | PubMed | ISI | ChemPort |
85.	Taub, M., Bonorris, G., Chung, A., Coyne, M. J. & Schoenfeld, L. J. Gastroenterology 72, 101−105 (1977). | PubMed | ISI | ChemPort |
86.	Cassuto, J., Jodal, M., Tuttle, R. & Lundgren, O. Experientia 35, 1467−1468 (1979). | PubMed | ISI | ChemPort |
87.	Lönnroth, I., Andrén, B., Lange, S., Martinsson, K. & Holmgren, J. Infect. Immunity 24, 900−905 (1979).
88.	Rabbani, G. H., Greenough, W. B. III, Holmgren, J. & Lönnroth, I. Lancet i, 410−412 (1979). | Article |
89.	Islam, M. R., Sack, D. A., Holmgren, J., Bardhan, P. K. & Lancet (submitted).
90.	Lönnroth, I. & Munck, B. G. Acta pharmac. tox. 47, 439−446 (1979).
91.	Smith, P. L. & Field, M. Gastroenterology 78, 1545−1553 (1980). | PubMed | ISI | ChemPort |
92.	Kakiuchi, S. & Rall, T. W. Molec. Pharmac. 4, 367−378 (1968). | ISI | ChemPort |
93.	Wolf, J. & Jones, A. B. Proc. natn. Acad. Sci. U.S.A. 65, 454−459 (1970).
94.	Cheung, W. Y., Lynch, T. J. & Wallace, R. W. Adv. Cyclic Nucleotide Res. 9, 233−251 (1978). | PubMed | ChemPort |
95.	Mata, L., Kronmal, R. A. & Villegas, H. in Cholera and Related Diarrhoeas: 43rd Nobel Symp., Stockholm 1978, 1−14 (Karger, Basel, 1980).
96.	Barua, D. in Nobel Conf. 3 (eds Holme, T., Holmgren, J., Merson, M. & Mollby, R.) (Elsevier, Amsterdam, in the press).
97.	Sack, R. B. A. Rev. Microbiol. 29, 333−353 (1975). | Article | ISI | ChemPort |
98.	Donta, S. T. & Smith, D. M. Infect. Immunity 9, 500−505 (1974). | ISI | ChemPort |
99.	Guerrant, R. L., Brunton, L. L., Schnaitman, T. C., Rebhun, L. I. & Gilman, A. G. Infect. Immunity 10, 320−327 (1974). | ISI | ChemPort |
100.	Yolken, R., Greenberg, H. B., Merson, M., Sack, R. B. & Kapikian, A. Z. J. clin. Microbiol. 6, 439−444 (1977). | PubMed | ISI | ChemPort |
101.	Svennerholm, A.-M. & Holmgren, J. Curr. Microbiol. 1, 19−27 (1978). | ISI | ChemPort |
102.	Sattler, J. et al. Eur. J. Biochem. 57, 309−316 (1975). | PubMed | ISI | ChemPort |
103.	Gill, D. M. Biochemistry 15, 1242−1248 (1976). | PubMed | ISI | ChemPort |
104.	Lai, C.-Y., Mendez, E. & Chang, D. J. infect. Dis. 133, S23−S30 (1976). | ISI |
105.	Kurosky, A., Markel, D. E. & Peterson, J. W. J. biol. Chem. 252, 7257−7264 (1977). | PubMed | ISI | ChemPort |
106.	Lai, C.-Y. J. biol. Chem. 252, 7249−7256 (1977). | PubMed | ISI | ChemPort |
107.	Sigler, P. B., Druyan, M. E., Kiefer, H. C. & Finkelstein, R. A. Science 197, 1277−1279 (1977). | PubMed | ISI | ChemPort |
108.	Gill, D. M. & Rappaport, R. S. J. infect. Dis. 139, 674−680 (1979). | PubMed | ISI | ChemPort |
109.	Tomasi, M., Battistini, A., Araco, A., Roda, L. G. & D'Agnolq, G. Eur. J. Biochem. 93, 621−627 (1979). | PubMed | ISI | ChemPort |
110.	Ohtomo, N., Muraoka, T., Tashiro, A., Zinnaka, Y. & Amako, K. J. infect. Dis. 133, (Suppl.), S31−S40 (1976). | ISI |
111.	Fishman, P. J., Moss, J., Richards, R. L., Brady, R. O. & Alving, C. R. Biochemistry 18, 2562−2567 (1979). | PubMed | ISI | ChemPort |
112.	Staerk, J., Ronneberger, H. J., Wiegandt, H. & Ziegler, W. Eur. J. Biochem. 48, 103−110 (1974). | PubMed | ISI | ChemPort |
113.	Haksar, A., Maudsley, D. V. & Péron, F. G. Nature 251, 514−515 (1974). | PubMed | ISI | ChemPort |
114.	Révész, T., Greaves, M. F., Capellaro, D. & Murray, R. K. Br. J. Haemat. 34, 623−630 (1976).
115.	Holmgren, J. in Bacterial Toxins and Cell Membranes (eds Jeljaszewicz, I. & Wadström, T.) 333−366 (Academic, London, 1978). | ChemPort |
116.	Craig, J. P. Nature 207, 614−616 (1965). | PubMed | ISI | ChemPort |
117.	Sack, R. B. in Nobel Conf. 3 (eds Holme, T., Holmgren, J., Merson, M. & Möllby, R.) (Elsevier, Amsterdam, in the press).
118.	Powell, D. W. & Field, M. in Secretory Diarrhoea (eds Field, M., Fordtran, J. S. & Schultz, S. G.) 187−209 (American Physiological Society, Maryland, 1980). | ChemPort |
119.	Jlundain, A. & Naftalin, R. J. Nature 279, 446−448 (1979).