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dc.contributor.author
Zampieri, Mattia
dc.contributor.author
Enke, Tim
dc.contributor.author
Chubukov, Victor
dc.contributor.author
Ricci, Vito
dc.contributor.author
Piddock, Laura
dc.contributor.author
Sauer, Uwe
dc.date.accessioned
2018-06-07T11:53:56Z
dc.date.available
2017-06-12T20:39:18Z
dc.date.available
2018-06-07T11:53:56Z
dc.date.issued
2017-03
dc.identifier.other
10.15252/msb.20167028
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/130031
dc.identifier.doi
10.3929/ethz-b-000130031
dc.description.abstract
Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint‐based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition‐dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome‐based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin‐resistant strains. Overall, resolving metabolic adaptation throughout antibiotic‐driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publ. Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Antibiotic resistance
en_US
dc.subject
Constraint-based modeling
en_US
dc.subject
Efflux pump
en_US
dc.subject
Evolution
en_US
dc.subject
Metabolism
en_US
dc.title
Metabolic constraints on the evolution of antibiotic resistance
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-03-06
ethz.journal.title
Molecular Systems Biology
ethz.journal.volume
13
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
917
en_US
ethz.size
14 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
004931271
ethz.publication.place
London
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
en_US
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.date.deposited
2017-06-12T20:40:34Z
ethz.source
ECIT
ethz.identifier.importid
imp593655606fc4d36372
ethz.ecitpid
pub:193032
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-14T15:38:57Z
ethz.rosetta.lastUpdated
2018-11-07T11:27:41Z
ethz.rosetta.versionExported
true
ethz.COinS
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