NEUTRALIZATION OF ISONIAZID ACTIVITY IN MYCOBACTERIUM TUBERCULOSIS BY CERTAIN METABOLITES

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Abstract
Pyridoxal was the most effective antagonist of the in vitro inhibitory effect of isoniazid on M. tuberculosis H37Rv. Others which demonstrated similar antagonism were pyridoxamine, sodium pyruvate, alpha-ketoglutarate, vitamin B12, guanine, nucleic acid, L-alanine, D-alanine, L-arginine, L-glutamic acid, D-glutamic acid, L-leucine, L-lysine, L-tyrosine, and DL-valine. Tubercle bacilli resistant to 10 [mu]g/ ml of isoniazid were markedly inhibited by the drug when tested in the presence of subinhibitory concentrations of pyridoxal. High concentrations of isoniazid inhibited the endogenous respiration of tubercle bacilli. This was overcome by pyridoxal or alpha-ketoglutarate, but not by pyruvate. Isoniazid inhibited the oxidation of pyruvate, lactate, acetate, glucose, and glycerol.