Altered methylation of ribosomal RNA in an erythromycin-resistant strain of Staphylococcus aureus

Abstract

In certain strains of Staphylococcus aureus, a concentration of erythromycin between 10(-8) and 10(-7) M can induce resistance to concentrations of this drug as high as 10(-4) M. In one such strain studied, S. aureus (1206), N(6)-dimethyladenine is not normally present in 23S rRNA; however, a compound presumptively identified (on the basis of paper chromatography in three different solvents) as N(6)-dimethyladenine appears in the 23S rRNA of growing cells that have been incubated in a medium containing 10(-7) M erythromycin. It has been shown previously that the induction of the erythromycin-resistant phenotype that occurs under these conditions requires 10(-8)-10(-7) M erythromycin for maximal expression within 1 hr and that induction results in modified 50S ribosomal subunits, which are then unable to bind erythromycin or lincomycin. Methylated adenine is also found in the 16S rRNA from the strain of S. aureus studied; however, in contrast to the situation with 23S rRNA, the amount in 16S rRNA is not affected by erythromycin. These findings provide the first example of a correlation between the methylation of rRNA and altered ribosomal function.