Restoration of mycolate synthetase activity in Mycobacterium tuberculosis exposed to isoniazid.

Cells of Mycobacterium tuberculosis H37Ra were pre-exposed to 0.5 p.g isoniazid (INH) per ml for GO min and waslH'cl. and the natllTe of restoration of cellular mycolate synthetase activity was stud­ ied upon reincubation. The restoration of this enzyme activity was a slow and gradual process in­ volving an 8-hour lag period and requiring about 24 hours' reincubation. The washed control cells also had an 8-hour lag period, but complete restoration occurred after about 10 to II hours. By subtracting the washing effect, the actual restoration time (a reversal of the INH effect) was about 14 hours. The INH inhibition of mycolate synthetase activity became irreversible when the ex­ posure time was IO hours or longer. Rifampin at 1.0 p.g per ml was shown to inhibit protein syn­ thesis in M. tuberculosis, but its effect on the mycolate synthetase activity was relatively moderate. Because rifampin did not effectively inhibit the restoration of mycolate synthetase activity, it was concluded that this restoration phenomenon did not involve protein synthesis.