Susceptibility of Mycobacterium tuberculosis to isoniazid and its derivative, 1-isonicotinyl-2-nonanoyl hydrazine:: investigation at cellular level

In this study, the susceptibility of Mycobacterium tuberculosis to isoniazid (INH) was compared with its derivative, 1-isonicotinyl-2-nonanoyl hydrazine (INH-C9), prepared synthetically. The minimum inhibitory concentration (MIC) of the drugs was determined using the 1% proportion method. INH-C9 was found to lower the MIC of INH from 0.05 to 0.025 mug/ml. Further studies on the effects of INH and INH-C9 on M. tuberculosis were assessed by exposing the cells to the above at the MIC level. A tuberculosis cells grown on Middlebrook 7H10 agar were harvested at different stages of their growth cycle (initial stage, 24 and 72 h), exposed to the MICs of INH and INH-C9, and stained with acid-fast staining. The observations were made for a week. The cellular morphologies and staining characteristics were examined using a Brightfield microscope. The result indicated cells only at the initial stage of growth were most susceptible to the drugs resulting in the loss of acid-fastness and intact cellular morphology in the majority of cells. (C) 2003 Published by Elsevier Ltd.