Action of Bacteriophage upon Production of in vivo Prepared Toxic Substance of Bacillus Typhosus. ∗

Abstract

In a previous communication 1 we reported the results of the inoculation of guinea pigs with the toxic material obtained from the exudate of experimental typhoid peritonitis. The filtered toxic material produced lesions closely simulating those of human typhoid fever and the animals died after 3 or 4 inoculations. The toxic substance produced in this manner was found to be of rather low potency. Single injections of from 3 to 5 cc. failed to produce death although the animals became sick and showed marked reactions to the inoculations.

It was thought that the employment of typhoid bacteriophage in conjunction with this in vivo method may serve the purpose of yielding a more toxic substance. It has already been shown that the action of bacteriophage in vitro has but little if any effect upon the toxicity of certain microorganisms. It was, however, thought that since the toxin employed previously by us was prepared in vivo, the presence of this lytic agent in the field of conflict between the host and the invading microorganism might provoke the liberation of a poison of more highly toxic nature.

Forty white mice and 24 guinea pigs were employed in the experiments. Typhoid culture 7D, a stock strain which had produced an accidental typhoid infection in one of us (Larimore) approximately a year ago and had been recovered from the blood stream, was employed for the inoculation. The typhoid bacteriophage used consisted of 2 separate “strains” kindly sent to us by Dr. D'Herelle and Dr. Bronfenbrenner.

Three sets of experiments were conducted: Series I consisted of the production of typhoid peritonitis in the mouse with the presence of varying amounts of phage introduced simultaneously with the infecting microorganism.