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dc.contributor.authorDolan, Stephen K
dc.contributor.authorKohlstedt, Michael
dc.contributor.authorTrigg, Stephen
dc.contributor.authorVallejo Ramirez, Pedro
dc.contributor.authorKaminski, Clemens F
dc.contributor.authorWittmann, Christoph
dc.contributor.authorWelch, Martin
dc.date.accessioned2020-02-13T00:30:32Z
dc.date.available2020-02-13T00:30:32Z
dc.date.issued2020-03-17
dc.identifier.issn2161-2129
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/302057
dc.description.abstractPseudomonas aeruginosa is an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile of P. aeruginosa appears to converge toward a common metabolic program as the organism adapts to the CF airway environment. However, we still have only a limited understanding of how these transcriptional changes impact metabolic flux at the systems level. To address this, we analyzed the transcriptome, proteome, and fluxome of P. aeruginosa grown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of an airway surfactant, phosphatidylcholine, which is known to be a major carbon source for P. aeruginosa in CF airways. We show that the fluxes of carbon throughout central metabolism are radically different among carbon sources. For example, the newly recognized "EDEMP cycle" (which incorporates elements of the Entner-Doudoroff [ED] pathway, the Embden-Meyerhof-Parnas [EMP] pathway, and the pentose phosphate [PP] pathway) plays an important role in supplying NADPH during growth on glycerol. In contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the reaction catalyzed by isocitrate dehydrogenase(s). Perhaps more importantly, our proteomic and transcriptomic analyses revealed a global remodeling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity of P. aeruginosa; that plasticity allows the organism to seamlessly segue between different carbon sources, maximizing the energetic yield from each.IMPORTANCEPseudomonas aeruginosa is an opportunistic human pathogen that is well known for causing infections in the airways of people with cystic fibrosis. Although it is clear that P. aeruginosa is metabolically well adapted to life in the CF lung, little is currently known about how the organism metabolizes the nutrients available in the airways. In this work, we used a combination of gene expression and isotope tracer ("fluxomic") analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We found that carbon is routed ("fluxed") through very different pathways during growth on these substrates and that this is accompanied by an unexpected remodeling of the cell's electron transfer pathways. Having access to this "blueprint" is important because the metabolism of P. aeruginosa is increasingly being recognized as a target for the development of much-needed antimicrobial agents.
dc.description.sponsorshipThis work was funded by a grant (BB/M019411/1) awarded to MW from the BBSRC. ST was supported by a BBSRC DTP studentship. CFK acknowledges funding from the UK Engineering and Physical Sciences Research Council, EPSRC (grants EP/L015889/1 and EP/H018301/1), the Wellcome Trust (grants 3-3249/Z/16/Z and 089703/Z/09/Z) and the UK Medical Research. 678 Council, MRC (grants MR/K015850/1 and MR/K02292X/1).
dc.format.mediumElectronic
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsAll rights reserved
dc.subjectPseudomonas aeruginosa
dc.subjectCarbon
dc.subjectAcetates
dc.subjectGlucose
dc.subjectGene Expression Profiling
dc.subjectProteomics
dc.subjectAdaptation, Physiological
dc.subjectGlycolysis
dc.subjectPentose Phosphate Pathway
dc.titleContextual Flexibility in Pseudomonas aeruginosa Central Carbon Metabolism during Growth in Single Carbon Sources.
dc.typeArticle
prism.issueIdentifier2
prism.publicationDate2020
prism.publicationNamemBio
prism.volume11
dc.identifier.doi10.17863/CAM.49132
dcterms.dateAccepted2020-01-30
rioxxterms.versionofrecord10.1128/mBio.02684-19
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-03-17
dc.contributor.orcidDolan, Stephen K [0000-0002-7391-2137]
dc.contributor.orcidVallejo Ramirez, Pedro [0000-0002-7879-6761]
dc.contributor.orcidKaminski, Clemens F [0000-0002-5194-0962]
dc.contributor.orcidWittmann, Christoph [0000-0002-7952-985X]
dc.identifier.eissn2150-7511
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M019411/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/H018301/1)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
pubs.funder-project-idMedical Research Council (MR/K015850/1)
pubs.funder-project-idMedical Research Council (MR/K02292X/1)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/L015889/1)
cam.issuedOnline2020-03-17
cam.orpheus.successTue Feb 01 18:59:16 GMT 2022 - Embargo updated
rioxxterms.freetoread.startdate2020-03-17


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