Certain properties of isoniazid inhibition of mycolic acid synthesis in cell-free systems of M. aurum and M. avium.

In Mycobacterium tuberculosis isoniazid (INH)-susceptibility and the presence of a thermolabile catalase-peroxidase (T-catalase) are nearly always associated. It is shown in this study that an INH-susceptible strain of M. aurum had a T-catalase activity while its resistant mutants did not, but an in vitro susceptible strain of M. avium had a strong catalase activity without any detectable peroxidase properties. Synthesis of mycolic acids is a genus-specific target for INH and there is an excellent parallelism between INH-susceptibility of intact cells and that of a cell-free system synthesizing mycolic acids. We investigated whether the INH-inhibition of mycolic acid cell-free synthesis was dependent on a T-catalase activity in M. aurum and M. avium: no catalase activity was detectable in any of the cell-free systems tested, and addition of T-catalase from susceptible M. aurum strain to an INH-resistant system did not render it sensitive. So INH can inhibit mycolic acid synthesis independently of the presence of a T-catalase. An INH-susceptible cell-free system prepared from INH-treated (at the MIC) cells 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.