Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Front Cell Infect Microbiol. 2023 Dec 8;13:1306567. doi: 10.3389/fcimb.2023.1306567. eCollection 2023.
Human trichinellosis is a parasitic infection caused by roundworms belonging to the genus , especially . Early and accurate clinical diagnoses of trichinellosis are required for efficacious prognosis and treatment. Current drug therapies are limited by antiparasitic resistance, poor absorption, and an inability to kill the encapsulating muscle-stage larvae. Therefore, reliable biomarkers and drug targets for novel diagnostic approaches and anthelmintic drugs are required. In this study, metabolite profiles of adult worms and muscle larvae were obtained using mass spectrometry-based metabolomics. In addition, metabolite-based biomarkers of excretory-secretory products and their related metabolic pathways were characterized. The metabolic profiling identified major, related metabolic pathways involving adenosine monophosphate (AMP)-dependent synthetase/ligase and glycolysis/gluconeogenesis in adult worms and muscle larvae, respectively. These pathways are potential drug targets for the treatment of the intestinal and muscular phases of infection. The metabolome of larva excretory-secretory products was characterized, with amino acid permease and carbohydrate kinase being identified as key metabolic pathways. Among six metabolites, decanoyl-l-carnitine and 2,3-dinor-6-keto prostaglandin F1α-d9 were identified as potential metabolite-based biomarkers that might be related to the host inflammatory processes. In summary, this study compared the relationships between the metabolic profiles of two growth stages. Importantly, the main metabolites and metabolic pathways identified may aid the development of novel clinical diagnostics and therapeutics for human trichinellosis and other related helminthic infections.
人旋毛虫病是一种寄生虫感染，由属于 属的圆线虫引起，尤其是 。早期和准确的临床诊断旋毛虫病对于有效的预后和治疗是必要的。目前的药物治疗受到抗寄生虫耐药性、吸收不良和无法杀死包囊肌肉阶段幼虫的限制。因此，需要可靠的生物标志物和药物靶点用于新的诊断方法和驱虫药物。在这项研究中，使用基于质谱的代谢组学获得了 成虫和肌肉幼虫的代谢物图谱。此外，还对 排泄-分泌产物的代谢物生物标志物及其相关代谢途径进行了表征。代谢组学分析确定了主要的相关代谢途径，涉及 成虫和肌肉幼虫中的腺苷一磷酸（AMP）依赖性合成酶/连接酶和糖酵解/糖异生，分别。这些途径是治疗肠道和肌肉感染阶段的潜在药物靶点。幼虫排泄-分泌产物的代谢组学特征，鉴定出氨基酸渗透酶和碳水化合物激酶是关键的代谢途径。在六种代谢物中，癸酰基-l-肉碱和 2,3-二降-6-酮前列腺素 F1α-d9 被鉴定为潜在的代谢物生物标志物，可能与宿主炎症过程有关。总之，本研究比较了两种 生长阶段的代谢谱之间的关系。重要的是，所确定的主要代谢物和代谢途径可能有助于开发新的临床诊断和治疗人旋毛虫病和其他相关蠕虫感染的方法。
