ANTIBIOTIC SUBSTANCES ACTIVE AGAINST M. TUBERCULOSIS

¹ Departments of Pharmacology and Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee

A mold identified as a strain of Aspergillus flavus Link has been isolated and when grown on a peptone-lactose medium has been found to produce a culture fluid which inhibits M. tuberculosis, S. aureus, and E. coli in vitro.

Antibiotic material has been extracted from this culture fluid at low pH by organic solvents (benzene or heptane).

This extract yields a mixture of organic acids which has antibiotic activity in vitro against a wide variety of both gram negative and gram positive bacteria, and against a number of acid-fast organisms. Activity is also shown against a strain of monilia. The properties of the crude antibiotic material are very similar to those described for aspergillic acid.

Fractionation procedures involving multiple extractions and recrystallizations have led to the isolation of an apparently pure aspergillic acid-like substance, m.p. 96.5-97.5° corr., in 5% yield, and a fraction m.p. 118-121° having about 75% the antibiotic activity, the same neutralization equivalent (230) and pK' (5.5) as the substance of m.p. 96.5-97.5.

There is good evidence that at least one other somewhat less stable antibiotic substance is present in the crude mixture.

All these fractions seem to have a similar antibiotic activity against S. aureus, E. coli and M. tuberculosis, and the addition of blood to the medium greatly reduces this activity. The activity is not reduced by spinal fluid.

Studies on impure material have shown that the toxic effects and the antibiotic activity disappear rapidly after systemic or intrathecal administration (mice, dogs) and that antibiotic material is excreted in urine (dog) in very small amount.