The author reported in previous papers that the isoniazid-resistant strains of tubercle bacilli or of atypical mycobacteria incorporated less amount of
14C-isoniazid than the isoniazid-sensitive strains, in non-growing but actively metabolizing state.
This paper deals with the incorporati on of
14Cisoniazid into the isoniazid-resistant and isoniazidsensitive strains of mycobacteria at the growing phase, and the investigation of the metabolism of
14C-isoniazid in these microbes.
When the isoniazid-sensitive strain of Mycobacterium tuberculosis H
37R
v was grown in the Tween 8O synthetic medium not containing isoniazid for 10 days at 37°C, followed by further cultivation in the same medium containing 2 mcg/ml of 14C-isoniazid for 7 days at 37°C, more than 10 times amount of
14C-isoniazid was incorporated into the cells, as compared with the case when the isoniazidresistant strains were cultured with the same procedure. Contents of
14C-isoniazid in the cell-free extract of isoniazid-sensitive strain was also much higher than that of isoniazid-resistant ones, as in the case of whole cells.
When these cell-free extracts were fractionated with trichloroacetic acid, almost all radioactivity of
14C-isoniazid was found in the acid-soluble fraction rather than in the acid-insoluble fraction.
From these results, it is suggeste d that the action of isoniazid to sensitive mycobacteria is the inhibition of biochemical activity of acid-soluble substance, probaly of a coenzyme, rather than the inactivation of active site of an enzyme, and that the mechanism of the isoniazid-resistance depends on smaller incorporation of isoniazid by the resistant strains, probably due to the decreased permeability of cell-surface (cytoplasmic membrane)against isoniazid.
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