23S Ribosomal RNA mutations in halobacteria conferring resistance to the anti-80S ribosome targeted antibiotic anisomycin

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Abstract
Halobacteriurn (H.) halob1ium and H. cutirubrura mutants res1stant To The anti-80S ribosome targeted inhibitor anisomycin were isolated. Three classes of mutants were obtained: Class I displayed a minimal Inhibitory concentration (MIC) to anisomycin of 10 μg/ml, class II of 25 μg/ml and class III of at least 400 μg/ml. In vitro polyphenylalan1ne synthesis assays demonstrated that 1n those cases tested resistance was a property of the large ribosomal subunit. By primer extension analysis, each mutation class could be correlated with a distinct base change within the peptidyl-transferase loop of 23S rRNA. In class I A2472 was changed to C, in class II G2466 was changed to C and in the high-level resistant class III C2471 was replaced by U. A double mutant -obtained by selection of a class I mutant for high-level anisoraycin resistance - acquired the C2471 to U replacement of class III 1n addition to the class I mutation. The results provide information on the action of a eukaryotic protein synthesis inhibitor on archaebacterial rbosomes and demonstrate the suitability of organisms with a single rRNA transcriptional unit on the chromosome for direct selection of mutations 1n ribosomal RNA.