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
ISSN
0027-8424
Recommended Citation
Moore, Sean D. and Sauer, Robert T., "Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22" (2008). Faculty Bibliography 2000s. 741.
https://stars.library.ucf.edu/facultybib2000/741
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