Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB

Eamonn Reading; Zainab Ahdash; Chiara Fais; Vito Ricci; Xuan Wang-Kan; Elizabeth Grimsey; Jack Stone; Giuliano Malloci; Andy M. Lau; Heather Findlay; Albert Konijnenberg; Paula J. Booth; Paolo Ruggerone; Attilio V. Vargiu; Laura J. V. Piddock; Argyris Politis

doi:10.1038/s41467-020-19397-2

Nature Communications (Nov 2020)

Perturbed structural dynamics underlie inhibition and altered efflux of the multidrug resistance pump AcrB

Eamonn Reading,
Zainab Ahdash,
Chiara Fais,
Vito Ricci,
Xuan Wang-Kan,
Elizabeth Grimsey,
Jack Stone,
Giuliano Malloci,
Andy M. Lau,
Heather Findlay,
Albert Konijnenberg,
Paula J. Booth,
Paolo Ruggerone,
Attilio V. Vargiu,
Laura J. V. Piddock,
Argyris Politis

Affiliations

Eamonn Reading: Department of Chemistry, King’s College London, Britannia House
Zainab Ahdash: Department of Chemistry, King’s College London, Britannia House
Chiara Fais: Department of Physics, University of Cagliari, Cittadella Universitaria, S.P. Monserrato-Sestu
Vito Ricci: Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham
Xuan Wang-Kan: Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham
Elizabeth Grimsey: Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham
Jack Stone: Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham
Giuliano Malloci: Department of Physics, University of Cagliari, Cittadella Universitaria, S.P. Monserrato-Sestu
Andy M. Lau: Department of Chemistry, King’s College London, Britannia House
Heather Findlay: Department of Chemistry, King’s College London, Britannia House
Albert Konijnenberg: Thermo Fisher Scientific
Paula J. Booth: Department of Chemistry, King’s College London, Britannia House
Paolo Ruggerone: Department of Physics, University of Cagliari, Cittadella Universitaria, S.P. Monserrato-Sestu
Attilio V. Vargiu: Department of Physics, University of Cagliari, Cittadella Universitaria, S.P. Monserrato-Sestu
Laura J. V. Piddock: Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham
Argyris Politis: Department of Chemistry, King’s College London, Britannia House

DOI: https://doi.org/10.1038/s41467-020-19397-2
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 11

Abstract

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AcrB is a prototypical resistance–nodulation–division (RND) bacterial transporter, conferring resistance to a variety of antibiotics. HDX-MS and other, complementary approaches offer insight into AcrB structural dynamics and suggest the molecular mechanisms underlying drug export and inhibition of this multidrug-resistance conferring pump.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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