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BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment

Mina, JG; Parthasarathy, A; Porta, EO; Denny, PW; Kalesh, K; (2024) BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment. Pathogens , 13 (10) , Article 879. 10.3390/pathogens13100879. Green open access

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Abstract

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’s 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.

Type: Article
Title: BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/pathogens13100879
Publisher version: https://doi.org/10.3390/pathogens13100879
Language: English
Additional information: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: BONCAT, Toxoplasma gondii, iTRAQ, pyrimethamine, quantitative proteomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10200157
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