Mina John G, Parthasarathy Anutthaman, Porta Exequiel O, Denny Paul W, Kalesh Karunakaran
Syngenta International Research Centre, Jealott's Hall, Bracknell, Berkshire RG42 6EY, UK.
School of Chemistry and Life Sciences, Richmond Building, University of Bradford, Bradford BD7 1DP, UK.
Pathogens. 2024 Oct 8;13(10):879. doi: 10.3390/pathogens13100879.
We employed a BONCAT-iTRAQ labelling approach to investigate newly synthesised proteins (NSPs) in 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 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 modulates its proteome in response to drug-induced stress and lay the groundwork for further investigations into potential therapeutic targets.
我们采用了生物正交非标准氨基酸标记与串联质谱标签（BONCAT-iTRAQ）标记方法，以研究在不同浓度的抗叶酸药物乙胺嘧啶作用下新合成的蛋白质（NSPs）。我们的结果表明，许多NSPs的表达水平因该药物而发生改变，在较高浓度下观察到显著上调。鉴定出了参与蛋白质合成、应激反应、能量代谢和细胞骨架动力学的关键蛋白质，表明[寄生虫名称未给出]对乙胺嘧啶治疗会产生复杂的适应性反应。虽然一些鉴定出的途径反映了一般的应激反应，但本研究提供了特定于寄生虫适应策略的重要分子标记和机制见解。这些发现有助于理解[寄生虫名称未给出]如何响应药物诱导的应激来调节其蛋白质组，并为进一步研究潜在治疗靶点奠定基础。
