ANALYSIS OF ISONIAZID-RESISTANT TRANSPOSON MUTANTS OF MYCOBACTERIUM-SMEGMATIS

The emergence of multidrug-resistant tuberculosis has renewed interest in the study of drug resistance in mycobacteria with the objective of improved chemotherapy. The genetic basis of isoniazid resistance in a model mycobacterium was studied. Eleven isoniazid-resistant mutants o f Mycobacterium smegmatis were created using transposon mutagenesis. G enetic and enzymatic characterisation of the mutants showed that katG, encoding T-catalase, was inactivated. The nucleotide sequence of M. s megmatis katG was determined and the mutation sites mapped demonstrati ng that both the amino and carboxyl halves of T-catalase an important for enzymatic activity.