Tuberculostatic Activity of Blood and Urine from Animals Given Gliotoxin

Abstract

Purified gliotoxin was found to inhibit growth of human and bovine tubercle bacilli in vitro when incorporated in various liquid culture media in concentrations of 0.012 to 0.06 micrograms/ml. It was much less active against a number of other bacterial species, the inhibitory concentrations ranging from 125 micrograms/ml for Ps. aeruginosa to 4.0 micrograms/ml for Pneumococcus, with intermediate concentrations required to inhibit several strains of Aerobacter aerogenes, Escherichia coli, Trichophyton gypseum, Streptococci, Staphylococcus aureus, and Bacillus subtilis. In this relation it is noteworthy that gliotoxin is highly active against several types of transplanted cancer cells in vitro, as previous work has shown; 1.0 microgram gliotoxin per ml regularly inhibited the subsequent growth in susceptible hosts of suspensions of Gardner lymphosarcoma cells, and concentrations of 5–25 micrograms gliotoxin per ml likewise inhibited the cells of several transplantable carcinomas of mice and rabbits (8, 15).Plasma procured from mice, guinea pigs, and rabbits within 30 minutes after they had been given gliotoxin orally or parenterally regularly inhibited growth of tubercle bacilli in dilutions as high as 1:320, and significant degrees of activity persisted for at least two hours in most instances. Urine collected from animals of the three species, two to three hours after they had been given gliotoxin, regularly inhibited growth of tubercle bacilli in dilutions from 1:320 to 1:1280. Plasma and urine procured from normal control animals of the three species had no tuberculostatic effect in concurrent tests.The course of experimental tuberculosis in C3H mice was not influenced in several experiments by the prolonged oral administration of purified gliotoxin in daily doses as high as 6.5 mg/kg.