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Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation
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dc.contributor.author | Odell, Anahi V. | |
dc.contributor.author | Tran, Fanny | |
dc.contributor.author | Foderaro, Jenna E. | |
dc.contributor.author | Poupart, Severine | |
dc.contributor.author | Pathak, Ravindra | |
dc.contributor.author | Westwood, Nicholas James | |
dc.contributor.author | Ward, Gary E. | |
dc.date.accessioned | 2015-03-20T17:01:18Z | |
dc.date.available | 2015-03-20T17:01:18Z | |
dc.date.issued | 2015-03-19 | |
dc.identifier.citation | Odell , 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.0120331 | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | PURE: 174236499 | |
dc.identifier.other | PURE UUID: 1e710679-5e00-40c1-be56-0a3a8d755c63 | |
dc.identifier.other | Scopus: 84925655103 | |
dc.identifier.other | ORCID: /0000-0003-0630-0138/work/56424149 | |
dc.identifier.other | WOS: 000351425400151 | |
dc.identifier.uri | https://hdl.handle.net/10023/6281 | |
dc.description | This 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 manuscript | en |
dc.description.abstract | Differentiation 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.iso | eng | |
dc.relation.ispartof | PLoS ONE | en |
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 credited | en |
dc.subject | Yeast three-hybrid | en |
dc.subject | Small-molecule | en |
dc.subject | Target identification | en |
dc.subject | Compound 2 | en |
dc.subject | Apicomplexa | en |
dc.subject | Parasite | en |
dc.subject | Toxoplasma gondii | en |
dc.subject | Bradyzoite | en |
dc.subject | QD Chemistry | en |
dc.subject | NDAS | en |
dc.subject.lcc | QD | en |
dc.title | Yeast three-hybrid screen identifies TgBRADIN/GRA24 as a negative regulator of Toxoplasma gondii bradyzoite differentiation | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Royal Society | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Chemistry | en |
dc.contributor.institution | University of St Andrews. EaSTCHEM | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0120331 | |
dc.description.status | Peer reviewed | en |
dc.identifier.url | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120331#sec025 | en |
dc.identifier.grantnumber | 516002.K5682/kk | en |
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