Pleiotropic Antibiotic Resistance Mutations Associated with Ribosomes and Ribosomal Subunits in Mycobacterium smegmatis

Viomycin-resistant strains isolated from Mycobacterium smegmatis demonstrated pleiotropic resistance to tuberactinomycin- N , capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance of three mutants isolated by stepwise selection for resistance to viomycin was due to alteration of the 30 S ribosomal subunit. One mutant, strain A, isolated independently by multiple-step selection to viomycin resistance, was resistant to viomycin, tuberactinomycin- N , and capreomycin through an alteration of the 50 S ribosomal subunit, whereas it was sensitive to kanamycin but resistant to streptomycin through an alteration of the 30 S ribosomal subunit. Three streptomycin-resistant strains, which were isolated by one-step selection at a high concentration of streptomycin, did not show significant co-resistance to any other antibiotics tested in culture and cell-free systems; streptomycin resistance in these mutants was localized on the 30 S ribosomal subunit.