Variation in Enterotoxigenicity of Escherichia coli

The possibility that the variable severity of diarrheal disease due to enterotoxigenic Escherichia coli might be explained by quantitative differences in the activity of heat-labile enterotoxin was examined. The amount of toxin secreted by 13 enteropathogenic strains of E. coli was quantitated by measurements of the toxin-dependent increase in adenosine 3':5'-cyclic phosphate (cyclic AMP) in Chinese hamster ovary cells. The activity ranged from 150 pmol of cyclic AMP/ml per mg of protein to 4,040 pmol/ml per mg. With three representative strains there was good correlation (r = -0.999; P less than 0.05) between the amounts of cyclic AMP accumulated intracellularly (4,040, 2,071, and 470 pmol of cyclic AMP/ml per mg of protein) and the ability of the filtrate to distend the rabbit ileal loop, as measured by the amounts of toxin required to produce half-maximal distension (50% effective dose, which had values of 11.5, 27.5, and 38.5 mg, respectively). The observed strain-to-strain variation in toxin activity may explain the variation in severity of diarrheal disease caused by enterotoxigenic E. coli.