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dc.contributor.authorOdell, Anahi V.
dc.contributor.authorTran, Fanny
dc.contributor.authorFoderaro, Jenna E.
dc.contributor.authorPoupart, Severine
dc.contributor.authorPathak, Ravindra
dc.contributor.authorWestwood, Nicholas James
dc.contributor.authorWard, Gary E.
dc.date.accessioned2015-03-20T17:01:18Z
dc.date.available2015-03-20T17:01:18Z
dc.date.issued2015-03-19
dc.identifier.citationOdell , A V , Tran , F , Foderaro , J E , Poupart , S , Pathak , R , Westwood , N J & Ward , G E 2015 , ' Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation ' , PLoS ONE , vol. 10 , no. 3 , e0120331 . https://doi.org/10.1371/journal.pone.0120331en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 174236499
dc.identifier.otherPURE UUID: 1e710679-5e00-40c1-be56-0a3a8d755c63
dc.identifier.otherScopus: 84925655103
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424149
dc.identifier.otherWOS: 000351425400151
dc.identifier.urihttp://hdl.handle.net/10023/6281
dc.descriptionThis work was supported by National Institutes of Health (NIH) grant AI054961 to GEW, and Royal Society University Research grant 516002.K5682/KK to NJW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
dc.description.abstractDifferentiation of the protozoan parasite Toxoplasma gondii into its latent bradyzoite stage is a key event in the parasite’s life cycle. Compound 2 is an imidazopyridine that was previously shown to inhibit the parasite lytic cycle, in part through inhibition of parasite cGMP-dependent protein kinase. We show here that Compound 2 can also enhance parasite differentiation, and we use yeast three-hybrid analysis to identify TgBRADIN/GRA24 as a parasite protein that interacts directly or indirectly with the compound. Disruption of the TgBRADIN/GRA24 gene leads to enhanced differentiation of the parasite, and the TgBRADIN/GRA24 knockout parasites show decreased susceptibility to the differentiation-enhancing effects of Compound 2. This study represents the first use of yeast three-hybrid analysis to study small-molecule mechanism of action in any pathogenic microorganism, and it identifies a previously unrecognized inhibitor of differentiation in T. gondii. A better understanding of the proteins and mechanisms regulating T. gondii differentiation will enable new approaches to preventing the establishment of chronic infection in this important human pathogen.
dc.language.isoeng
dc.relation.ispartofPLoS ONEen
dc.rights© 2015 Odell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are crediteden
dc.subjectYeast three-hybriden
dc.subjectSmall-moleculeen
dc.subjectTarget identificationen
dc.subjectCompound 2en
dc.subjectApicomplexaen
dc.subjectParasiteen
dc.subjectToxoplasma gondiien
dc.subjectBradyzoiteen
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subject.lccQDen
dc.titleYeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiationen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0120331
dc.description.statusPeer revieweden
dc.identifier.urlhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120331#sec025en


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