Relationship of Bacteriophage to Toxin and Antitoxin

Abstract

Some investigators have implied that bacteriophage action was identical to the action of toxin and antitoxin. d'Herelle suggested that bacteriophage was in fact an antitoxin. The observations on the clinical application of bacteriophage have awaited an adequate theoretical basis before they could be interpreted and a foundation laid for intelligent formulation of a rationale of treatment and prophylaxis. Staphylococcus toxin has only recently been developed to a point where it may be safely assumed that such a toxin exists, and where means of measuring its activity and potency have been sufficiently standardized to permit of fruitful study. Having then a satisfactory staphylococcus toxin and a bacteriophage highly active against staphylococci, the necessary elements for a study of the relationship between toxin and bacteriophage have become available. The following report is a preliminary study of this relationship from which it is believed definite conclusions can be drawn.

The production of staphylococcus toxin followed the method given by Dollman 1 and based upon the earlier work of Burnet^{2, 3} and his coworkers. Plates of beef extract broth to which 0.5% agar had been added were inoculated with staphylococcus and incubated for 48 hours in an atmosphere of 15% CO₂. The semifluid material after incubation was passed through filter paper, the reaction adjusted to pH 6.6 and 1 :8000 merthiolate was added. Six toxins were prepared in this manner and their potency tested first by hemolysis of rabbit red blood cells. The results are shown in Table I.

Bacteriophage itself incubated under similar conditions with rabbit red blood cells produced no hemolysis and hence has none of the hemolytic properties of staphylococcus toxin.