SUMMARY: Ribosomes of Streptomyces azureus, the thiostrepton producer, are resistant to the drug due to the action of an RNA-pentose methylase which acts on 23S ribosomal RNA. This enzyme, which is active in vitro on ribosomal RNA from other bacteria (e.g. Escherichia coli), employs S-adenosylmethionine as cofactor to catalyse the formation of a single residue of 2′-O-methyladenosine. The ‘thiostrepton-resistance methylase’ has been purified 11 000-fold (although not to homogeneity) and eluted from gel filtration columns with an apparent molecular weight of 35 000 to 38 000. The preferred substrate for the methylase was phenol-extracted 23S RNA. In contrast, mature 50S ribosomal subunits were unaffected by the enzyme although protein-deficient core particles, prepared by exposure of ribosomes to LiCl, retained partial substrate activity. Significantly, the methylase was inactive on the complex of 23S RNA with ribosomal protein L11.
BenvenisteR.,
DaviesJ.1973; Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proceedings of the National Academy of Sciences of the United States of America 70:2276–2280
DixonP.D.,
BevenJ.E.,
CundliffeE.1975; Properties of the ribosomes of antibiotic producers: effects of thiostrepton and micrococcin on the organisms which produce them. Antimicrobial Agents and Chemotherapy 7:850–855
HelserT.L.,
DaviesJ.E.,
DahlbergJ.E.1971; Change in methylation of 16S ribosomal RNA associated with mutation to kasugamycin resistance in Escherichia coli
. Nature New Biology 233:12–14
HomannH.E.,
NierhausK.H.1971; Ribosomal proteins.Protein compositions of biosynthetic precursors and artificial subparticles from ribosomal subunits in Escherichia coli K12. European Journal of Biochemistry 20:249–257
SkinnerR.H.,
CundliffeE.1980; Resistance to the antibiotics viomycin and capreomycin in the Streptomyces species which produce them. Journal of General Microbiology 120:95–104
ThompsonJ.,
CundliffeE.,
StarkM.1979; Binding of thiostrepton to a complex of 23S rRNA with ribosomal protein Lll. European Journal of Biochemistry 98:261–265
WeisblumB.1975; Altered methylation of ribosomal ribonucleic acid in erythromycin-resistant Staphylococcus aureus
. In Microbiology - 1974 pp. 199–206 Edited by
SchlessingerD.
Washington, D.C.: American Society for Microbiology.;