Abstract
In contrast to cholera enterotoxin and other Escherichia coli enterotoxins, a pig-specific, heat-stable E. coli enterotoxin (STb) causes morphologic lesions (loss of villous epithelial cells and partial villous atrophy). These lesions reflect a loss of absorptive cells and thus suggest that STb causes impaired absorption as well as inducing net secretion. The present studies assess functional significance of morphologic changes induced by STb. Net fluid movement, mucosal surface area, sucrase activity and the electrical response induced by alanine were measured in swine jejunal loops exposed to E. coli culture filtrates with and without STb. Net fluid secretion (-11.1±1.1 ml) occurred in some STb loops (secretors) and net absorption (2.7±0.3 ml) in others (nonsecretors), but net absorption occurred in all control loops (4.9±0.2 ml). The mucosal surface area of Stb loops was about 20% less than that of controls (P<0.01). Sucrase activity was also lower (about 15%) in STb loops than in control loops (P<0.01). The electrical response induced by alanine in mucosa from nonsecreting STb loops did not differ from that induced in mucosa from control loops. However, the response to alanine in mucosa from secreting STb loops was reduced about 70% from that in mucosa from nonsecreting STb loops or from control loops (P<0.05). It is concluded that reduced sucrase activity is a functional correlate to villous atrophy induced by STb, that STb impairs alanine absorption in some loops (secretors), and that the impaired alanine absorption is independent of the decreased surface area caused by Stb. Because the impaired alanine absorption occurred independent of the decreases in surface area, it is suggested that the secretory response to STb is associated with an impairment of active absorption of alanine.
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Alderete, J.F. and Robertson, D.C., 1978. Purification and chemical characterization of the heat-stable enterotoxin produced by porcine strains of enterotoxigenic Escherichia coli. Infect. Immun., 19: 1021–1030.
Argenzio, R.A., Liacos, J., Berschneider, H.M., Whipp, S.C., and Robertson, D.C., 1984. Effect of heat-stable enterotoxin of Escherichia coli and theophylline on ion transport in porcine small intestine. Can. J. Comp. Med., 48: 14–22.
Burgess, M.N., Bywater, R.J., Cowley, C.M., Mullan, N.A., and Newsome, P.M., 1978. Biological evaluation of a methanol-soluble, heat-stable Escherichia coli enterotoxin in infant mice, pigs, rabbits, and calves. Infect. Immun., 21: 526–531.
Bywater, R.J., 1972. Dialysis and ultrafiltration of a heat-stable enterotoxin from Escherichia coli. J. Med. Microbiol., 5: 337–343.
Dahlqvist, A., 1964. Method for assay of intestinal disaccharidases. Anal. Biochem., 7: 18–25.
Dauncey, M.J., Ingram, D.L., James, P.S., and Smith, M.W., 1983. Modification by diet and environmental temperature of enterocyte function in piglet intestine. J. Physiol., 341: 441–452.
Donta, S.T., King, M., and Sloper, K., 1973. Induction of steroidogenesis in tissue culture by cholera enterotoxin. Nature New Biol., 243: 246–247.
Dorner, F. and Mayer, P., 1975. Escherichia coli enterotoxin: stimulation of adenyl cyclase in broken-cell preparations. Infect. Immun., 11: 429–435.
Dunnill, M.S. and Whitehead, R., 1972. A method for the quantitation of small intestinal biopsy specimens. J. Clin. Path., 25: 243–256.
Elliot, H.L., Carpenter, C.C., Sack, R.B., and Yardley, J.H., 1970. Small bowel morphology in experimental canine cholera. A light and electron microscopic study. Lab. Invest., 22: 112–120.
Evans, D.J., Chen, L.C., Curlin, G.T., and Evans, D.G., 1972. Stimulation of adenyl cyclase by Escherichia coli enterotoxin. Nature New Biol., 236: 137–138.
Field, M., Graf, L.H.Jr., Laird, W.J., and Smith, P.L., 1978. Heatstable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration and ion transport in small intestine. Proc. Natl. Acad. Sci. USA, 75: 2800–2804.
Guerrant, R.L., Brunton, L.L., Schnaitman, T.C., Rebhun, L.I., and Gilman, A.G., 1974. Cyclic adenosine monophosphate and alteration of Chinese hamster ovary cell morphology: a rapid, sensitive in vitro assay for the enterotoxins of Vibrio cholerae and Escherichia coli. Infect. Immun., 10: 320–327.
Guerrant, R.L., Hughes, J.M., Chang, B., Robertson, D.C., and Murad, F., 1980. Activation of intestinal guanylate cyclase by heat-stable enterotoxin of Escherichia coli: studies of tissue specificity, potential receptors, and intermediates. J. Infect. Dis., 142: 220–228.
Guerrant, R.L. and Weikel, C.S., 1984. Pharmacologic pathways leading to intestinal secretion: stimulation by enterotoxins and by C-kinase activators. In: Proc. 20th Joint Conference on Cholera: U.S.-Japan Coop. Med. Sci. Prog. Cholera Panel, p. 39.
Gyles, C.L., 1979. Limitations of the infant mouse test for Escherichia coli heat-stable enterotoxin. Can. J. Comp. Med., 43: 371–379.
Gyles, C.L. and Barnum, D.A., 1969. A heat-labile enterotoxin from strains of Escherichia coli enteropathogenic for pigs. J. Infect. Dis., 120: 419–426.
Hewlett, E.L., Guerrant, R.L., Evans, D.J.Jr., and Greenough, W.B.III., 1974. Toxins of Vibrio cholerae and Escherichia coli stimulate adenyl cyclase in rat fat cells. Nature, 249: 371–373.
Hughes, J.M., Murad, F., Chang, B., and Guerrant, R.L., 1978. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature, 271: 755–756.
Kashiwazaki, M., Akaike, Y., Miyachi, T., Ogawa, T., Sugawaram, M., and Isayama, Y., 1981a. Production of heat-stable enterotoxic component by Escherichia coli strains enteropathogenic for swine. Natl. Inst. Animal Health Q. (Jpn), 21: 21–25.
Kashiwazaki, M., Nakamura, K., Sugimoto, C., Isayama, Y., and Akaike, Y., 1981b. Diarrhea in piglets due to Escherichia coli that produce only porcine ileal loop-positive heat-stable enterotoxic component. Natl. Inst. Animal Health Q (Jpn), 21: 148–149.
Kennedy, D.J., Greenberg, R.N., Dunn, J.A., Abernathy, R., Ryerse, J.S., and Guerrant, R.L., 1984. Effects of Escherichia coli heat-stable enterotoxin STb on intestines of mice, rats, rabbits, and piglets. Infect. Immun., 46: 639–643.
Kohler, E.M., 1971. Observations on enterotoxins produced by enteropathogenic Escherichia coli. Ann. New York Acad. Sci., 176: 212–219.
Kohler, E.M. and Cross, R.F., 1969. Studies of Escherichia coli in gnotobiotic pigs. VI. Effects of feeding bacteria-free filtrates of broth cultures. Can. J. Comp. Med., 33: 173–177.
Lee, C.H., Moseley, S.L., Moon, H.W., Whipp, S.C., Gyles, C.L., and So, M., 1983. Characterization of the gene encoding heat-stable toxin II and preliminary molecular epidemiologic studies of enterotoxigenic Escherichia coli heat-stable toxin II producers. Infect. Immun., 42: 264–268.
Moon, H.W., Fung, P.Y., Whipp, S.C., and Isaacson, R.E., 1978. Effects of age and ambient temperature on the response of infant mice to heat-stable enterotoxin of Escherichia coli: Assay modifications. Infect. Immun., 20: 36–39.
Moon, H.W., Whipp, S.C., and Baetz, A.L., 1971. Comparative effects of enterotoxins from Escherichia coli and Vibrio cholerae on rabbit and swine small intestine. Lab. Invest., 25: 133–140.
Olsson, E. and Soderlind, O., 1980. Comparison of different assays for definition of heat-stable enterotoxigenicity of Escherichia coli porcine strains. J. Clin. Microbiol., 11: 6–15.
Picken, R.N., Mazaitis, A.J., Maas, W.K., Rey, M., and Heyneker, H., 1983. Nucleotide sequence of the gene for heat-stable enterotoxin II of Escherichia coli. Infect. Immun., 42: 269–275.
Rao, M.C., Guandalini, S., Smith, P.L., and Field, M., 1980. Mode of action of heat stable Escherichia coli enterotoxin. Biochim. et Biophys. Acta, 632: 35–46.
Smith, H.W. and Halls, S., 1967. Studies on Escherichia coli enterotoxin. J. Pathol. Bacteriol., 93: 531–543.
So, M. and McCarthy, B.J., 1980. Nucleotide sequence of the bacterial transposon Tn 1681 encoding a heat-stable (ST) toxin and its identification in enterotoxigenic Escherichia coli strains. Proc. Natl. Acad. Sci. USA, 77: 4011–4015.
Weibel, E.R., 1963. Principles and methods for the morphometric study of lung and other organs. Lab. Invest., 12: 131–135.
Weikel, C.S. and Guerrant, R.L., 1985. STb enterotoxin of Escherichia coli: cyclic nucleotide-independent secretion. In: Guerrant, R.L. (ed.), Microbial Toxins and Diarrhoeal Disease. Pitman, Ondon, CIBA Foundation Symposium 112.
Weikel, C.S., Long-Krug, S.A. and Guerrant, R.L., 1983. E. coli STb: A new mechanism for secretory diarrhea? In: Proc. 19th Joint Conference on Cholera: U.S.-Japan Coop. Med. Sci. Prog. Cholera Panel, pp. 91–92.
Whipp, S.C., Moon, H.W., and Argenzio, R.A., 1981. Comparison of enterotoxic activities of heat-stable enterotoxins from class 1 and class 2 Escherichia coli of swine origin. Infect. Immun., 31: 245–251.
Whipp, S.C., Moon, H.W., Kemeny, L.J., and Argenzio, R.A., 1985. Effect of virus-induced destruction of villous epithelium on intestinal secretion induced by heat-stable Escherichia coli enterotoxins and prostaglandin E1 in swine. Am. J. Vet. Res., 46: 637–642.
Whipp, S.C., Moon, H.W., and Moseley, S.L., 1986. Histologic alterations induced in jejunal mucosa by Escherichia coli pig-specific, mouse-negative, heat-stable enterotoxin (STb). Am. J. Vet. Res. (in press)
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Whipp, S.C., Kokue, E., Morgan, R.W. et al. Functional significance of histologic alterations induced by Escherichia coli pig-specific, mouse-negative, heat-stable enterotoxin (STb). Veterinary Research Communications 11, 41–55 (1987). https://doi.org/10.1007/BF00361325
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DOI: https://doi.org/10.1007/BF00361325