{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:18Z","timestamp":1760146218404,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/P027989\/1A","RGS\\R2\\222343"],"award-info":[{"award-number":["MR\/P027989\/1A","RGS\\R2\\222343"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["MR\/P027989\/1A","RGS\\R2\\222343"],"award-info":[{"award-number":["MR\/P027989\/1A","RGS\\R2\\222343"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We employed a BONCAT-iTRAQ labelling approach to investigate newly synthesised proteins (NSPs) in Toxoplasma gondii subjected to varying concentrations of the antifolate drug pyrimethamine. Our results reveal that numerous NSPs exhibited altered expression levels in response to the drug, with significant upregulation observed at higher concentrations. Key proteins involved in protein synthesis, stress responses, energy metabolism, and cytoskeletal dynamics were identified, indicating that T. gondii undergoes complex adaptive responses to pyrimethamine treatment. While some of the identified pathways reflect a generic stress response, this study provides important molecular markers and mechanistic insights specific to the parasite\u2019s adaptation strategies. These findings contribute to understanding how T. gondii modulates its proteome in response to drug-induced stress and lay the groundwork for further investigations into potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/pathogens13100879","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T12:01:54Z","timestamp":1728388914000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-1370","authenticated-orcid":false,"given":"John G.","family":"Mina","sequence":"first","affiliation":[{"name":"Syngenta International Research Centre, Jealott\u2019s Hall, Bracknell, Berkshire RG42 6EY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1830-5948","authenticated-orcid":false,"given":"Anutthaman","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"School of Chemistry and Life Sciences, Richmond Building, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7463-1468","authenticated-orcid":false,"given":"Exequiel O.","family":"Porta","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University College London, London WC1N 1AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-1613","authenticated-orcid":false,"given":"Paul W.","family":"Denny","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-3992","authenticated-orcid":false,"given":"Karunakaran","family":"Kalesh","sequence":"additional","affiliation":[{"name":"School of Health and Life Sciences, Teesside University, Middlesbrough TS1 3BX, UK"},{"name":"National Horizons Centre, 38 John Dixon Lane, Darlington DL1 1HG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Heppler, L.N., Attarha, S., Persaud, R., Brown, J.I., Wang, P., Petrova, B., Tosic, I., Burton, F.B., Flamand, Y., and Walker, S.R. 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