Pathogenesis of Experimental Cholera: Biologic Activities of Purified Procholeragen A

Abstract
Procholeragen A, a choleragenic moiety elaborated by Vibrio cholerae 569 B Inaba, has been concentrated and partially purified by gel filtration with Sephadex G-200. Purified Procholeragen A, which is essentially free of cholera endotoxin but still not pure, gives a single zone of precipitation with rabbit anti-choleragen antibody adsorbed with live vibrios and causes experimental cholera when amounts as little as 6.0-µg are administered, with Procholeragen B, per os in infant rabbits. When inoculated intradermally in adult rabbits in 0.1 to 0.2-µg amounts, it causes a delayed but sustained local erythematous edematous induration which fixes intravenous Evans blue dye. Procholeragen B, which was formerly considered to be essential for the activity of Procholeragen A, simply serves to protect the latter against destruction under acid conditions in the stomach and can be replaced by a variety of buffers. Procholeragen A causes experimental cholera when inoculated, by itself, into the small bowel of infant rabbits. On the basis of the experimental observations, it is suggested, as an operational concept, that an increase of villus capillary permeability, as a consequence of the direct action of a Procholeragen A-like factor elaborated by cholera vibrios in the small intestines, is a major factor in the pathogenesis of cholera.