Conversion of Cholera Exo-Enterotoxin (Choleragen) to Natural Toxoid (Choleragenoid)

The phenomenon of spontaneous conversion of bacterial toxins to toxoids has been observed since the time of Ehrlich although information regarding the mechanism of the reaction is limited. The toxoiding process, apparently common to many protein toxins, occurs on aging and may be accelerated by chemical treatment such as with formaldehyde. In the latter case, a different molecular species of toxoid may result. For example, spontaneously formed tetanus toxoid has been reported to be a dimer of the toxin, whereas the formaldehyde toxoid can be similar in size to the parent toxin (1–4). In some instances, notably among other clostridia, toxin may be released into the medium in the form of a protoxin that is antigenically similar to the toxin but lacks toxicity. The protoxin is converted into toxin by bacterial proteases (5). Previous work in this laboratory has led to the isolation and purification of the cholera exoenterotoxin, designated choleragen, from vigorously aerated and agitated multi-liter fermenter cultures of Vibrio cholerae 569B (6, 7).