CHARACTERIZATION OF THE KATG GENE ENCODING A CATALASE-PEROXIDASE REQUIRED FOR THE ISONIAZID SUSCEPTIBILITY OF MYCOBACTERIUM-TUBERCULOSIS

The isoniazid susceptibility of Mycobacterium tuberculosis is mediated by the product of the katG gene which encodes the heme-containing enz yme catalase-peroxidase. In this study, the chromosomal location of ka tG has been established and its nucleotide sequence has been determine d so that the primary structure of catalase-peroxidase could be predic ted. The M. tuberculosis enzyme is an 80,000-dalton protein containing several motifs characteristic of peroxidases and shows strong similar ity to other bacterial catalase-peroxidases. Expression of the katG ge ne in M. tuberculosis, M. smegmatis, and Escherichia coli was demonstr ated by Western blotting (immunoblotting). Homologous genes were detec ted in other mycobacteria, even those which are naturally insensitive to isoniazid.