Relationship of Pyridoxine and its Derivatives to the Mechanism of Action of Isoniazid.

Abstract

1. It was possible to inhibit growth of organisms other than Mycobacterium with isoniazid by controlling the amount of pyridoxine and its derivatives in the media. Lactobacillus plantarum and Saccharomyces carlsbergensis were inhibited in a synthetic medium by isoniazid concentrations of less than 10² M. This inhibition was competitively reversed by pyridoxine, pyridox-amine, and pyridoxal. In reversing isoniazid inhibition of Lactobacillus, pyridoxamine, and pyridoxal were from 1000 to 4000 times more effective, than pyridoxine. 2. Two strains of E. coli were inhibited with isoniazid with partial reversal with pyridoxine and derivatives. Larger amounts of the metabolite were required and the reversal was not as typically competitive. 3. No reversal of isoniazid inhibition could be obtained with vit. B₆ or its derivatives in any of the Mycobacteria tested. If isoniazid acts as an antagonist of pyridoxine or its derivatives in the Mycobacteria, it is not a simple substrate competition or uptake phenomenon.