Sharkey, LKR, Edwards, TA and O'Neill, AJ (2016) ABC-F proteins mediate antibiotic resistance through ribosomal protection. mBio, 7 (2). e01975-15.
Abstract
Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to an in vitro translation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosome in vitro. To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Sharkey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Mar 2016 12:19 |
Last Modified: | 10 Nov 2018 10:37 |
Published Version: | http://dx.doi.org/10.1128/mBio.01975-15 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/mBio.01975-15 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:95600 |