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Mutations in Domain II of 23 S rRNA Facilitate Translation of a 23 S rRNA-encoded Pentapeptide Conferring Erythromycin Resistance

https://doi.org/10.1006/jmbi.1996.0296Get rights and content

Abstract

Mutations in domain II ofEscherichia coli23 S rRNA that cause resistance to erythromycin do so in a manner fundamentally different from mutations at the drug binding site in domain V of the 23 S rRNA. The domain II mutations are located in a hairpin structure between nucleotides 1198 and 1247. This is close to a short open reading frame in the 23 S rRNA that encodes a pentapeptide (E-peptide) whose expressionin vivorenders cells resistant to erythromycin. Therefore, a possible mechanism of resistance caused by domain II mutations may be related to an increased expression of the E-peptide. To test this hypothesis, a range of point mutations was generated in domain II of 23 S rRNA in the vicinity of the E-peptide open reading frame. We find a correlation between erythromycin resistance of the mutant clones and increased accessibility of the ribosome binding site of the E-peptide gene. Furthermore, the erythromycin resistance determinant in the mutants was shown to be confined to a small 23 S rRNA segment containing the coding region and the ribosome binding site of the E-peptide open reading frame. It thus appears that the domain II mutations mediate erythromycin resistance by increasing expression of the 23 S rRNA-encoded E-peptide.

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Permanent address: T. Tenson, Institute of Molecular and Cellular Biology, Tartu University, Tartu, Estonia.

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