Isoniazid perturbation of the pyridine nucleotide cycle of Escherichia coli.
Isogenic strains of Escherichia coli, differing only in their sensitivity/resistance to isoniazid, were compared on the basis of intracellular accumulation of the intermediates of the pyridine nucleotide cycle and a closely related compound, nicotinamide adenine dinucleotide phosphate. Isoniazid treatment was bacteriostatic for the wild type organism and resulted in an exaggerated lag phase followed by a rapid logarithmic growth rate in the isoniazid-resistant strain. Isoniazid treatment of the wild type strain, even in the absence of growth, resulted in a temporal shift of peak pyridine accumulation from early lag phase to early logarithmic phase. The effect of mutation from isoniazid sensitivity to isoniazid resistance was accompanied by this same temporal shift of peak pyridine accumulation. In addition, mutation was accompanied by increases in the peak concentrations, as compared to wild type, of desamidonicotinamide adenine dinucleotide, nicotinamide, nicotinic acid and nicotinamide mononucleotide; the levels of nicotinic acid mononucleotide, nicotinamide adenine dinucleotide phosphate and nicotinamide adenine dinucleotide were decreased. Isoniazid treatment of the isoniazid-resistant strain, even in the absence of bacteriostasis, caused a decrease in the intracellular concentrations of nicotinic acid and nicotinamide and an increase in nicotinic acid mononucleotide. Isoniazid treatment of both the sensitive and resistant strains resulted in the loss of a peak ratio of NADP to NAD which normally occurred in the late logarithmic/early stationary phase of growth in untreated cultures. This denoted a loss of ability to shift from the generation of energy from glycolysis to generation of energy from the hexose monophosphate shunt.
D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D007538:Isoniazid / Q000494:pharmacology*; D009154:Mutation; D009243:NAD / Q000031:analogs & derivatives / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D009525:Niacin / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives / Q000378:metabolism
D009243:NAD; D009537:Nicotinamide Mononucleotide; D009536:Niacinamide; D009525:Niacin; C002953:nicotinate mononucleotide; D009249:NADP; C018348:nicotinic acid adenine dinucleotide; D007538:Isoniazid