EFFECT OF ENZYME INHIBITORS AND ACTIVATORS ON THE MULTIPLICATION OF TYPHUS RICKETTSIAE : I. PENICILLIN, PARA-AMINOBENZOIC ACID, SODIUM FLUORIDE, AND VITAMINS OF THE B GROUP

By injection into typhus-infected yolk sacs, a number of agents were tested for possible inhibition or acceleration of rickettsial growth. The previously reported rickettsiostatic activity of penicillin was further confirmed. Para-aminobenzoic acid, in single injections of 6.6 mg. and 3.3 mg. giving initial concentrations of approximately 1:6000 and 1:12,000 was found to have rickettsiostatic activity approximately equal to that of penicillin. No conclusion could be drawn regarding the possibility of a synergistic action of para-aminobenzoic acid and penicillin. Para-aminobenzoic acid neutralized with sodium hydroxide was found to be as effective as the acid itself, when given in single injections of 6.6 mg. Sodium benzoate, as Well as the ortho and meta forms of aminobenzoic acid were found to be ineffective when given in similar amounts. Para-aminobenzoic acid, when added to the food in a concentration of 3 per cent, was shown to have a remarkably effective chemotherapeutic action on murine typhus infection in mice. Sodium fluoride was found at times to accelerate the growth of rickettsiae in the yolk sac, and to cause heavy infection under conditions such that the controls showed practically no multiplication of the organism. When rickettsiostatic substances (penicillin and para-aminobenzoic acid) were combined with sodium fluoride, their rickettsiostatic activity was not demonstrably changed. Other agents studied and found not to affect rickettsial multiplication are listed. The possible mechanisms involved in the observed inhibition and stimulation of rickettsial growth under these conditions are discussed.