Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS Negl Trop Dis. 2021 Sep 2;15(9):e0009706. doi: 10.1371/journal.pntd.0009706. eCollection 2021 Sep.
Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment.
METHODOLOGY/PRINCIPAL FINDINGS: Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.
湄公血吸虫病是一种由寄生在血液中的吸虫湄公血吸虫引起的寄生虫病。这种疾病导致湄公地区的人类发病率和死亡率上升，对该地区的人民构成了公共卫生威胁。目前，吡喹酮（PZQ）是治疗湄公血吸虫病的首选药物。然而，PZQ 作用的分子机制尚不清楚，并且偶尔会报道湄公血吸虫对 PZQ 的耐药性。通过这项研究，我们旨在使用代谢组学方法来鉴定与 PZQ 治疗相关的湄公血吸虫中潜在改变的代谢途径。
方法/主要发现：将成年阶段的湄公血吸虫在体外分别用 0、20、40 或 100μg/mL 的 PZQ 处理。在暴露于 PZQ 一个小时后，提取血吸虫代谢物并用质谱法进行研究。用 XCMS 在线平台对治疗组的代谢组学数据进行分析，并与未处理组的数据进行比较。在低、中（IC50）和高剂量 PZQ 后，我们发现 1007 种代谢物发生了变化，其中磷脂酰丝氨酸和花生四烯酸酰胺是通过多变量和两两分析得出的主要差异代谢物。在途径分析中，发现花生四烯酸代谢在 PZQ 处理后发生改变，表明该途径可能受到药物的影响，并可能被认为是抗血吸虫病药物开发的新靶点。
结论/意义：我们的研究结果表明，花生四烯酸代谢可能是 PZQ 对湄公血吸虫的驱虫作用的潜在靶点。确定有效药物 PZQ 的潜在靶点为发现和开发新的药物提供了一个有趣的观点，这些药物可能增强血吸虫病的预防和治疗。
