CERTAIN PROPERTIES OF ISONIAZID INHIBITION OF MYCOLIC ACID SYNTHESIS IN CELL-FREE SYSTEMS OF M-AURUM AND MYCOBACTERIUM-AVIUM

In Mycobacterium tuberculosis isoniazid (INH)-susceptibility and the p resence of a thermolabile catalase-peroxidase (T-catalase) are nearly always associated. It is shown in this study that an INH-susceptible s train of M. aurum had a T-catalase activity while its resistant mutant s did not, but an in vitro susceptible strain of M. avium had a strong catalase activity without any detectable peroxidase properties. Synth esis of mycolic acids is a genus-specific target for INH and there is an excellent parallelism between INH-susceptibility of intact cells an d that of a cell-free system synthesizing mycolic acids. We investigat ed whether the INH-inhibition of mycolic acid cell-free synthesis was dependent on a T-catalase activity in nil. aurum and M. avium: no cata lase activity was detectable in any of the cell-free systems tested, a nd addition of T-catalase from susceptible M. aurum strain to an INH-r esistant system did not render it sensitive. So INH can inhibit mycoli c acid synthesis independently of the presence of a T-catalase. An INH -susceptible cell-free system prepared from INH-treated (at the MIC) c ells was progressively and irreversibly inhibited, while incubation of the same susceptible system in the presence of INH did not result in a significant irreversible inhibition. The possible participation of T -catalase in the irreversible effect of INH is discussed.