Targeting pathogen metabolism without collateral damage to the host

dc.contributor.authorHaanstra, Jurgen R.en_ZA
dc.contributor.authorGerding, Alberten_ZA
dc.contributor.authorDolga, Amalia M.en_ZA
dc.contributor.authorSorgdrager, Freek J. H.en_ZA
dc.contributor.authorBuist-Homan, Manonen_ZA
dc.contributor.authorDu Toit, Francoisen_ZA
dc.contributor.authorFaber, Klaas Nicoen_ZA
dc.contributor.authorHolzhutter, Hermann-Georgen_ZA
dc.contributor.authorSzoor, Balazsen_ZA
dc.contributor.authorMatthews, Keith R.en_ZA
dc.contributor.authorSnoep, Jacky L.en_ZA
dc.contributor.authorWesterhoff, Hans V.en_ZA
dc.contributor.authorBakker, Barbara M.en_ZA
dc.identifier.citationHaanstra, J. R., et al. 2017. Targeting pathogen metabolism without collateral damage to the host. Scientific Reports, 7:40406, doi:10.1038/srep40406en_ZA
dc.identifier.issn2045-2322 (online)
dc.descriptionCITATION: Haanstra, J. R., et al. 2017. Targeting pathogen metabolism without collateral damage to the host. Scientific Reports, 7:40406, doi:10.1038/srep40406.en_ZA
dc.descriptionThe original publication is available at https://www.nature.comen_ZA
dc.description.abstractThe development of drugs that can inactivate disease-causing cells (e.g. cancer cells or parasites) without causing collateral damage to healthy or to host cells is complicated by the fact that many proteins are very similar between organisms. Nevertheless, due to subtle, quantitative differences between the biochemical reaction networks of target cell and host, a drug can limit the flux of the same essential process in one organism more than in another. We identified precise criteria for this ‘network-based’ drug selectivity, which can serve as an alternative or additive to structural differences. We combined computational and experimental approaches to compare energy metabolism in the causative agent of sleeping sickness, Trypanosoma brucei, with that of human erythrocytes, and identified glucose transport and glyceraldehyde-3-phosphate dehydrogenase as the most selective antiparasitic targets. Computational predictions were validated experimentally in a novel parasite-erythrocytes co-culture system. Glucose-transport inhibitors killed trypanosomes without killing erythrocytes, neurons or liver cells.en_ZA
dc.format.extent15 pages : illustrationsen_ZA
dc.publisherNature Researchen_ZA
dc.subjectPathogen metabolismen_ZA
dc.subjectDrug safetyen_ZA
dc.subjectCancer -- Treatment -- Complicationsen_ZA
dc.subjectInfectious diseases -- Treatment -- Complicationsen_ZA
dc.titleTargeting pathogen metabolism without collateral damage to the hosten_ZA
dc.description.versionPublisher's versionen_ZA
dc.rights.holderAuthors retain copyrighten_ZA

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