SUMMARY: The effect of various substrates on the oxygen uptake of Mycobacterium smegmatis grown in the presence of glucose and glycerol was investigated; isoniazid had no effect on these oxidations. Three different effects of isoniazid on the metabolism of this organism were demonstrated, (i) Growth of the organism in a minimal medium in the Warburg apparatus was prevented by the addition of isoniazid, the amount required being related to the number of organisms present, their age and their sensitivity to the drug as measured by serial dilution in the test tube, (ii) In confirmation of the report of Zeller, Barsky, Berman & Fouts (1952) it was found that isoniazid inhibited the oxidation of putrescine by M. smegmatis. (iii) Following the work of Gray (1953) the effect of isoniazid on the oxidation of various substrates by M. smegmatis grown in the absence of glucose and glycerol was studied. Isoniazid caused a 30 % inhibition of the oxidation of acetate. The amount of isoniazid required to inhibit the oxidation of putrescine and acetate was the same whether the strain used was sensitive or resistant to isoniazid as measured by growth in the test tube.
In an attempt to discover the mechanism by which isonicotinic acid hydrazide (isoniazid) inhibits the growth of mycobacteria, the effect of isoniazid on their respiration was investigated. Preliminary work involved a study of the oxidative metabolism of the saprophytic organism Mycobacterium smegmatis.
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