Inhibition by Isoniazid of Synthesis of Mycolic Acids in Mycobacterium tuberculosis

SUMMARY Exposure of growing Mycobacterium tuberculosis bcg to 1 µ g. isoniazid/ml. inhibited the incorporation of 14C from [U-14C] and [2-14C]glycerol and [1-14C]- glutamate into its walls by about 50 % over 12 h. because 14C incorporation into the mycolic acids of the walls was prevented. Isoniazid, 0·5 µ g. / ml. with M. tuberculosis bcg or 0·1 µ g./ml. with M. tuberculosis H37 Ra, inhibited incorporation of 14C from [U-14C] glycerol into total mycolic acids by about 90 % 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 M. tuberculosis 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.