THE RPSL GENE AND STREPTOMYCIN RESISTANCE IN SINGLE AND MULTIPLE DRUG-RESISTANT STRAINS OF MYCOBACTERIUM-TUBERCULOSIS

The recent emergence of indolent and rapidly fatal drug-resistant stra ins of Mycobacterium tuberculosis has renewed interest in defining the molecular mechanisms of drug resistance in the tubercle bacilli. In t his report, we have examined the mechanism of resistance to streptomyc in (Sm) in M. tuberculosis through the cloning and nucleotide sequence analysis of the gene encoding the ribosomal S12 protein (rpsL gene) f rom streptomycin-resistant strains and their streptomycin-sensitive pa rental strains. We have demonstrated that five singly Sm(R) M. tubercu losis strains and an Sm(R) isolate that has reduced sensitivity to mul tiple antibiotics have identical point mutations at codon 43 of the rp sL gene. Mutations at this same site confer Sm(R) in Escherichia coli. In contrast, two other multiple drug-resistant M. tuberculosis strain s that are resistant to Sm have rpsL genes that have the same nucleoti de sequence as their drug-sensitive parent strains, suggesting that di fferent resistance mechanisms are involved in these strains.