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dc.contributor.author
Zimmermann, Michael
dc.contributor.author
Kogadeeva, Maria
dc.contributor.author
Gengenbacher, Martin
dc.contributor.author
McEwen, Gayle
dc.contributor.author
Mollenkopf, Hans-Joachim
dc.contributor.author
Zamboni, Nicola
dc.contributor.author
Kaufmann, Stefan Hugo Ernst
dc.date.accessioned
2017-11-15T15:46:49Z
dc.date.available
2017-10-06T03:05:50Z
dc.date.available
2017-11-15T15:46:49Z
dc.date.issued
2017-08-22
dc.identifier.other
10.1128/mSystems.00057-17
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/191307
dc.identifier.doi
10.3929/ethz-b-000191307
dc.description.abstract
Nutrient acquisition from the host environment is crucial for the survival of intracellular pathogens, but conceptual and technical challenges limit our knowledge of pathogen diets. To overcome some of these technical roadblocks, we exploited an experimentally accessible model for early infection of human macrophages by Mycobacterium tuberculosis, the etiological agent of tuberculosis, to study host-pathogen interactions with a multi-omics approach. We collected metabolomics and complete transcriptome RNA sequencing (dual RNA-seq) data of the infected macrophages, integrated them in a genome-wide reaction pair network, and identified metabolic subnetworks in host cells and M. tuberculosis that are modularly regulated during infection. Up- and downregulation of these metabolic subnetworks suggested that the pathogen utilizes a wide range of host-derived compounds, concomitant with the measured metabolic and transcriptional changes in both bacteria and host. To quantify metabolic interactions between the host and intracellular pathogen, we used a combined genome-scale model of macrophage and M. tuberculosis metabolism constrained by the dual RNA-seq data. Metabolic flux balance analysis predicted coutilization of a total of 33 different carbon sources and enabled us to distinguish between the pathogen’s substrates directly used as biomass precursors and the ones further metabolized to gain energy or to synthesize building blocks. This multiple-substrate fueling confers high robustness to interventions with the pathogen’s metabolism. The presented approach combining multi-omics data as a starting point to simulate system-wide host-pathogen metabolic interactions is a useful tool to better understand the intracellular lifestyle of pathogens and their metabolic robustness and resistance to metabolic interventions.
en_US
dc.language.iso
en
en_US
dc.publisher
American Society for Microbiology
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
systems biology
en_US
dc.subject
host-pathogen interactions
en_US
dc.subject
metabolism
en_US
dc.subject
Mycobacterium tuberculosis
en_US
dc.title
Integration of Metabolomics and Transcriptomics Reveals a Complex Diet of Mycobacterium tuberculosis during Early Macrophage Infection
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
MSYSTEMS
ethz.journal.volume
2
en_US
ethz.journal.issue
4
en_US
ethz.pages.start
e00057-17
en_US
ethz.size
18 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Washington, DC
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::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::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::03713 - Sauer, Uwe / Sauer, Uwe
ethz.date.deposited
2017-10-06T03:06:05Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-02-01T09:35:29Z
ethz.rosetta.lastUpdated
2018-11-06T01:42:21Z
ethz.rosetta.versionExported
true
ethz.rosetta.versionExported
true
ethz.COinS
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