Exposure of growing BCG to 1 μg. isoniazid/ml. inhibited the incorporation of C from [U-C] and [2-C]glycerol and [I-C]-glutamate into its walls by about 50% over 12 h. because C incorporation into the mycolic acids of the walls was prevented. Isoniazid, 0.5 μg./ml. with BCG or 0.1μg.ml. with H37Ra, inhibited incorporation of C from [U-C]glycerol into total mycolic acids by about 99% over 6 h., indicating that inhibition began within 1 h. of the addition of the drug. There was no effect on mycolic acid synthesis in an isoniazid-resistant strain of BCG. The primary inhibitory action of isoniazid in sensitive mycobacteria is probably on mycolic acid synthesis, and this leads to formation of defective boundary layers of the bacteria.


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