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dc.contributor.author
Zampieri, Mattia
dc.contributor.author
Zimmermann, Michael
dc.contributor.author
Claassen, Manfred
dc.contributor.author
Sauer, Uwe
dc.date.accessioned
2017-12-05T14:15:17Z
dc.date.available
2017-10-06T02:19:53Z
dc.date.available
2017-11-02T14:18:43Z
dc.date.available
2017-11-02T14:19:48Z
dc.date.available
2017-12-05T14:15:17Z
dc.date.issued
2017-05-09
dc.identifier.issn
2666-3864
dc.identifier.issn
2211-1247
dc.identifier.other
10.1016/j.celrep.2017.04.002
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/190670
dc.identifier.doi
10.3929/ethz-b-000190670
dc.description.abstract
Microbes have shown a remarkable ability in evading the killing actions of antimicrobial agents, such that treatment of bacterial infections represents once more an urgent global challenge. Understanding the initial bacterial response to antimicrobials may reveal intrinsic tolerance mechanisms to antibiotics and suggest alternative and less conventional therapeutic strategies. Here, we used mass spectrometry-based metabolomics to monitor the immediate metabolic response of Escherichia coli to a variety of antibiotic perturbations. We show that rapid metabolic changes can reflect drug mechanisms of action and reveal the active role of metabolism in mediating the first stress response to antimicrobials. We uncovered a role for ammonium imbalance in aggravating chloramphenicol toxicity and the essential function of deoxythymidine 5′-diphosphate (dTDP)-rhamnose synthesis for the immediate transcriptional upregulation of GyrA in response to quinolone antibiotics. Our results suggest bacterial metabolism as an attractive target to interfere with the early bacterial response to antibiotic treatments and reduce the probability for survival and eventual evolution of antibiotic resistance.
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
E. coli
en_US
dc.subject
antibiotic response
en_US
dc.subject
metabolomics
en_US
dc.subject
antibiotic tolerance
en_US
dc.subject
dTDP-rhamnose
en_US
dc.subject
ammonium imbalance
en_US
dc.subject
quinolones
en_US
dc.subject
chloramphenicol
en_US
dc.title
Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2017-05-09
ethz.journal.title
Cell Reports
ethz.journal.volume
19
en_US
ethz.journal.issue
6
en_US
ethz.journal.abbreviated
Cell Rep
ethz.pages.start
1214
en_US
ethz.pages.end
1228
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
New York, NY
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03984 - Claassen, Manfred (ehemalig) / Claassen, Manfred (former)
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03713 - Sauer, Uwe / Sauer, Uwe
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03984 - Claassen, Manfred (ehemalig) / Claassen, Manfred (former)
ethz.date.deposited
2017-10-06T02:19:57Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-12-05T14:15:29Z
ethz.rosetta.lastUpdated
2021-02-14T21:08:43Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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