CORE
🇺🇦
make metadata, not war
Services
Services overview
Explore all CORE services
Access to raw data
API
Dataset
FastSync
Content discovery
Recommender
Discovery
OAI identifiers
OAI Resolver
Managing content
Dashboard
Bespoke contracts
Consultancy services
Support us
Support us
Membership
Sponsorship
Community governance
Advisory Board
Board of supporters
Research network
About
About us
Our mission
Team
Blog
FAQs
Contact us
Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding
Authors
AAA Antwi
D Barker
+12 more
P Bernal
JMA Blair
L Dortet
RCD Furniss
D Gonzalez
N Kaderabkova
GJ Larrouy-Maumus
E Maslova
DAI Mavridou
RR McCarthy
HE McNeil
HL Pugh
Publication date
13 January 2022
Publisher
'eLife Sciences Publications, Ltd'
Doi
View
on
PubMed
Abstract
Data availability: All data generated during this study that support the findings are included in the manuscript or in the Supplementary Information.Copyright © 2022, Furniss et al. Antimicrobial resistance in Gram-negative bacteria is one of the greatest threats to global health. New antibacterial strategies are urgently needed, and the development of antibiotic adjuvants that either neutralize resistance proteins or compromise the integrity of the cell envelope is of ever-growing interest. Most available adjuvants are only effective against specific resistance proteins. Here we demonstrate that disruption of cell envelope protein homeostasis simultaneously compromises several classes of resistance determinants. In particular, we find that impairing DsbA-mediated disulfide bond formation incapacitates diverse β-lactamases and destabilizes mobile colistin resistance enzymes. Furthermore, we show that chemical inhibition of DsbA sensitizes multidrug-resistant clinical isolates to existing antibiotics and that the absence of DsbA, in combination with antibiotic treatment, substantially increases the survival of Galleria mellonella larvae infected with multidrug-resistant Pseudomonas aeruginosa. This work lays the foundation for the development of novel antibiotic adjuvants that function as broad-acting resistance breakers.MRC Career Development Award MR/M009505/1 (to D.A.I.M.); the institutional BBSRC-DTP studentships BB/M011178/1 (to N.K.) and BB/M01116X/1 (to H.L.P.); the BBSRC David Philips Fellowship BB/M02623X/1 (to J.M.A.B.); the ISSF Wellcome Trust grant 105603/Z/14/Z (to G.L.-M.); the Brunel Research Innovation and Enterprise Fund, Innovate UK and British Society for Antimicrobial Chemotherapy grants 2018-11143, 37800 and BSAC-2018-0095, respectively (to R.R.MC); the Swiss National Science Foundation Postdoc Mobility and Ambizione Fellowships P300PA_167703 and PZ00P3_180142, respectively (to D.G.)
Similar works
Full text
Open in the Core reader
Download PDF
Available Versions
Sustaining member
Brunel University Research Archive
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:bura.brunel.ac.uk:2438/240...
Last time updated on 07/02/2022
University of Birmingham Research Portal
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:pure.atira.dk:openaire_cri...
Last time updated on 28/12/2022
University of Birmingham Research Portal
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:pure.atira.dk:publications...
Last time updated on 28/12/2022