III. MODE OF ACTION OF ANTITUBERCULOSIS DRUGS ON TUBERCLE BACILLI

Electron Microscopic Study and Biosynthetic Study

Abstract

Mode of action of antituberculosis drugs was studied by electron microscopy and biochemical methods.
1) Fine structure of tubercle bacilli treated with kanamycin revealed disappearence of normal structure of ribosome and aggregation of the cytoplasm. By biochemical study, it was observed that kanamycin inhibits polypeptide synthesis, followed by the break down of polysomes and detachment of m-RNA.
2) Fine structure of tubercle bacilli treated with rifampicin revealed marked changes in the cytoplasm such as loss of compact structure of ribosomes. Destruction of mesosomes and condensation of nucleoid were also observed. The cytoplasmic membrane and the cell wall were well preserved. By biochemical study, purified DNA-dependent RNA polymerase prepared from BCG, inhibited 70% of activity of RNA polymerase at a concentration of 0.1μg per ml. Rifampicin seemed to affect the initiation of chain formation in RNA synthesis.
3) Fine structure of tubercle bacilli treated with ethambutol revealed the characteric changes in nuclear region. Numerous vesicles and a little fiber structures of DNA were seen in the nucleus.
4) Fine structure of tubercle bacilli treated with isoniazid revealed the numerous vesicles in the nucleus. Fiber structures of DNA are scarecely observed. Cell wall and cytoplasm are not affected. By biochemical methods, thymidine uptake of bacilli seemed to be affected by isoniazid.
5) Fine structure of tubercle bacilli treated with cycloserine revealed the destruction of cell walls. By ruthenium red staining, it was assumed that peptidglycan of cell wall was damaged.