Protection of Escherichia coli from Isoniazid Inhibition

Abstract

Inhibition of Escherichia coli by isonicotinic acid hydrazide (isoniazid) is a function of the initial cell concentration, concentration of antibiotic, and chemical composition of the medium. An initial concentration of 5 × 10 5 cells/ml in a minimal medium is inhibited by 1 mM isoniazid. The E. coli cells are protected from this inhibitory effect by a high concentration of cells in the medium. Protection is also obtained from vitamin-free Casamino Acids, methionine, or choline plus homocystine. However, nicotinic acid, nicotinamide, and pyridoxamine are not able to reverse the effect of isoniazid. Colonies arising on minimal medium supplemented with isoniazid are not due to selection of resistant mutants, because this resistance is transitory and not passed on to the daughter cells. It is hypothesized that this transitory resistance is a manifestation of the cells' ability to transfer the methyl group of methionine to either isoniazid or accumulated nicotinic acid and/or nicotinamide.