MOLECULAR MECHANISMS OF MULTIPLE-DRUG RESISTANCE IN CLINICAL ISOLATESOF MYCOBACTERIUM-TUBERCULOSIS

The molecular mechanisms of resistance to streptomycin, rifampin, and isoniazid in 53 Mycobacterium tuberculosis clinical isolates were exam ined, Twenty-five of 44 streptomycin-resistant strains had mutations i n the rpsL gene and 5 of these had rus gene perturbations, The region of the rpoB gene that is associated with resistance to rifampin was al tered in 28 of 29 rifampin-resistant strains, Mutations in known genet ic markers of isoniazid resistance were detected in 25 of 42 isoniazid -resistant isolates: 20 strains had katG gene alterations and 5 had pe rturbations in the inhA operon. Of the 20 multiply resistant strains w ith reduced sensitivity to streptomycin, rifampin, and isoniazid, 11 h ad mutations in genetic markers associated with resistance to each of these three drugs, These studies suggest that the primary mechanism of multiple drug resistance in tuberculosis is the accumulation of mutat ions in individual drug target genes.