Golizeh Makan, Nam John, Chatelain Eric, Jackson Yves, Ohlund Leanne B, Rasoolizadeh Asieh, Camargo Fabio Vasquez, Mahrouche Louiza, Furtos Alexandra, Sleno Lekha, Ndao Momar
Department of Mathematical and Physical Sciences, Concordia University of Edmonton, Edmonton, Alberta, Canada.
National Reference Centre for Parasitology, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
Heliyon. 2022 Dec 15;8(12):e12380. doi: 10.1016/j.heliyon.2022.e12380. eCollection 2022 Dec.
The causative agent of Chagas disease (CD), , claims thousands of lives each year. Current diagnostic tools are insufficient to ensure parasitological detection in chronically infected patients has been achieved. A host-derived metabolic signature able to distinguish CD patients from uninfected individuals and assess antiparasitic treatment efficiency is introduced. Serum samples were collected from chronic CD patients, prior to and three years after treatment, and subjected to untargeted metabolomics analysis against demographically matched CD-negative controls. Five metabolites were confirmed by high-resolution tandem mass spectrometry. Several database matches for sex steroids were significantly altered in CD patients. A murine experiment corroborated sex steroid perturbation in -infected mice, particularly in male animals. Proteomics analysis also found increased steroidogenesis in the testes of infected mice. Metabolic alterations identified in this study shed light on the pathogenesis and provide the basis for developing novel assays for the diagnosis and screening of CD patients.
恰加斯病(CD)的病原体每年夺去数千人的生命。目前的诊断工具不足以确保已实现对慢性感染患者的寄生虫学检测。本文介绍了一种能够区分CD患者与未感染个体并评估抗寄生虫治疗效果的宿主衍生代谢特征。收集慢性CD患者治疗前和治疗三年后的血清样本,并针对人口统计学匹配的CD阴性对照进行非靶向代谢组学分析。通过高分辨率串联质谱法确认了五种代谢物。CD患者中几种与性类固醇的数据库匹配结果有显著改变。一项小鼠实验证实了感染小鼠体内的性类固醇紊乱,特别是在雄性动物中。蛋白质组学分析还发现感染小鼠睾丸中的类固醇生成增加。本研究中确定的代谢改变揭示了发病机制,并为开发用于诊断和筛查CD患者的新检测方法提供了基础。