Title

Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22

Authors

Authors

S. D. Moore;R. T. Sauer

Comments

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Abstract

Bacterial antibiotic resistance can occur by many mechanisms. An intriguing class of mutants is resistant to macrolide antibiotics even though these drugs still bind to their targets. For example, a 3-residue deletion (Delta MKR) in ribosomal protein L22 distorts a loop that forms a constriction in the ribosome exit tunnel, apparently allowing nascent-chain egress and translation in the presence of bound macrolides. Here, however, we demonstrate that Delta MKR and wild-type ribosomes show comparable macrolide sensitivity in vitro. In Escherichia coli, we find that this mutation reduces antibiotic occupancy of the target site on ribosomes in a manner largely dependent on the AcrAB-TolC efflux system. We propose a model for antibiotic resistance in which Delta MKR ribosomes alter the translation of specific proteins, possibly via changes in programmed stalling, and modify the cell envelope in a manner that lowers steady-state macrolide levels.

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

Volume

105

Issue/Number

47

Publication Date

1-1-2008

Document Type

Article

First Page

18261

Last Page

18266

WOS Identifier

WOS:000261489300042

ISSN

0027-8424

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