Inhibition by isoniazid of synthesis of mycolic acids in Mycobacterium tuberculosis.

Exposure of growing Mycobacterium tuberculosis BCG to I pg. isoniazid/ml. inhibited the incorporation of 14C from [U-14C] and [2-1*C]glycerol and [ 1-14C]glutamate into its walls by about 50 :A over I 2 h. because 14C incorporation into the mycolic acids of the walls was prevented. Isoniazid, 0.5 ,ug./ml. with M. tuberculosis BCG or 0.1 pg./ml. with M. tuberculosis ~ 3 7 R a , inhibited incorporation of 14C from [U-14C]glycerol into total mycolic acids by about 90 yo over 6 h., indicating that inhibition began within I h. of the addition of the drug. There was no effect on mycolic acid synthesis in an isoniazidresistant 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.