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2014-07-17Zeitschriftenartikel DOI: 10.1371/journal.ppat.1004263
BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei
dc.contributor.authorOppenheim, Rebecca D.
dc.contributor.authorCreek, Darren J.
dc.contributor.authorMacrae, James I.
dc.contributor.authorModrzynska, Katarzyna K.
dc.contributor.authorPino, Paco
dc.contributor.authorLimenitakis, Julien
dc.contributor.authorPolonais, Valerie
dc.contributor.authorSeeber, Frank
dc.contributor.authorBarrett, Michael P.
dc.contributor.authorBillker, Oliver
dc.contributor.authorMcConville, Malcolm J.
dc.contributor.authorSoldati-Favre, Dominique
dc.date.accessioned2018-05-07T17:50:40Z
dc.date.available2018-05-07T17:50:40Z
dc.date.created2014-08-15
dc.date.issued2014-07-17none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/re48MuW4i1yos/PDF/27ykk0wyT2JU.pdf
dc.identifier.urihttp://edoc.rki.de/176904/1933
dc.description.abstractWhile the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectMitochondria/enzymologyeng
dc.subjectMitochondria/geneticseng
dc.subjectMitochondrial Proteins/geneticseng
dc.subjectOxidoreductases/geneticseng
dc.subjectPlasmodium berghei/enzymologyeng
dc.subjectPlasmodium berghei/geneticseng
dc.subjectProtozoan Proteins/geneticseng
dc.subjectToxoplasma/enzymologyeng
dc.subjectToxoplasma/geneticseng
dc.subject.ddc610 Medizin
dc.titleBCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10037205
dc.identifier.doi10.1371/journal.ppat.1004263
dc.identifier.doihttp://dx.doi.org/10.25646/1858
local.edoc.container-titlePLoS ONE
local.edoc.container-textOppenheim RD, Creek DJ, Macrae JI, Modrzynska KK, Pino P, et al. (2014) BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei. PLoS Pathog 10(7): e1004263.
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004263
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume10
local.edoc.container-issue7
local.edoc.container-year2014

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