CsrA maximizes expression of the AcrAB multidrug resistance transporter

Vito Ricci; Victoria Attah; Tim Overton; David C. Grainger; Laura J. V. Piddock

doi:10.1093/nar/gkx929

CsrA maximizes expression of the AcrAB multidrug resistance transporter

Vito Ricci, Victoria Attah, Tim Overton, David C. Grainger, Laura J. V. Piddock

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Abstract

Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins. Given the role of AcrAB-TolC in multi-drug efflux we suggest that CsrA is a potential drug target.

Original language	English
Pages (from-to)	12798–12807
Journal	Nucleic Acids Research
Volume	45
Issue number	22
Early online date	13 Oct 2017
DOIs	https://doi.org/10.1093/nar/gkx929
Publication status	Published - 15 Dec 2017

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10.1093/nar/gkx929Licence: Creative Commons: Attribution-NonCommercial (CC BY-NC)

RicciV2017CsrA
This article has been accepted for publication in Nucleic Acids Research ©: The Author(s) 2017, Published by Oxford University Press on behalf of Nucleic Acids Research. All rights reserved.
Final published version, 2.1 MBLicence: Creative Commons: Attribution-NonCommercial (CC BY-NC)

Unravelling Multiple Antibiotic Resistance in Salmonella Enterica
Piddock, L. (Principal Investigator)
Medical Research Council
1/04/06 → 31/03/09
Project: Research Councils

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title = "CsrA maximizes expression of the AcrAB multidrug resistance transporter",

abstract = "Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins. Given the role of AcrAB-TolC in multi-drug efflux we suggest that CsrA is a potential drug target.",

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AU - Ricci, Vito

AU - Attah, Victoria

AU - Overton, Tim

AU - Grainger, David C.

AU - Piddock, Laura J. V.

PY - 2017/12/15

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AB - Carbon Storage Regulator A (CsrA) is an RNA binding protein that acts as a global regulator of diverse genes. Using a combination of genetics and biochemistry we show that CsrA binds directly to the 5' end of the transcript encoding AcrAB. Deletion of csrA or mutagenesis of the CsrA binding sites reduced production of both AcrA and AcrB. Nucleotide substitutions at the 5' UTR of acrA mRNA that could potentially weaken the inhibitory RNA secondary structure, allow for more efficient translation of the AcrAB proteins. Given the role of AcrAB-TolC in multi-drug efflux we suggest that CsrA is a potential drug target.

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DO - 10.1093/nar/gkx929

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EP - 12807

JO - Nucleic Acids Research

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IS - 22

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CsrA maximizes expression of the AcrAB multidrug resistance transporter

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Unravelling Multiple Antibiotic Resistance in Salmonella Enterica

Cite this