Mechanism of Action of Isoniazid on Mycobacterium bovis Strain BCG

The mechanism of action of isoniazid (INH) on Mycobacterium bovis strain BCG was studied. The rates of synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein after the addition of INH to growing cultures were followed by measuring the incorporation of (3)H-thymidine, (3)H-uridine, and (14)C-l-valine, respectively. After the addition of INH, the rate of DNA synthesis began to decrease and was abolished within 4 hr. RNA synthesis ceased after 6 hr, and protein synthesis was inhibited after 7 hr. Thus, it appears that inhibition of the synthesis of DNA is one of the earliest events after INH addition. The inhibition of the synthesis of DNA was further found to correspond to losses in viability of treated cultures. Degradation of preexisting DNA in INH-treated strain BCG was not detected.