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

Mina, John G.; Parthasarathy, Anutthaman; Porta, Exequiel O.; Denny, Paul W.; Kalesh, Karunakaran

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.

Citation

Mina, J. G., Parthasarathy, A., Porta, E. O., Denny, P. W., & Kalesh, K. (2024). BONCAT-iTRAQ Labelling Reveals Molecular Markers of Adaptive Responses in Toxoplasma gondii to Pyrimethamine Treatment. Pathogens, 13(10), Article 879. https://doi.org/10.3390/pathogens13100879

• Journal Article Type: Article
• Acceptance Date: Oct 7, 2024
• Online Publication Date: Oct 8, 2024
• Publication Date: Oct 1, 2024
• Deposit Date: Oct 10, 2024
• Publicly Available Date: Oct 10, 2024
• Journal: Pathogens
• Electronic ISSN: 2076-0817
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 10
• Article Number: 879
• DOI: https://doi.org/10.3390/pathogens13100879
• Keywords: Toxoplasma gondii, pyrimethamine, quantitative proteomics, iTRAQ, BONCAT
• Public URL: https://durham-repository.worktribe.com/output/2952724