State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, People's Republic of China.
Department of Parasitology, Shandong University School of Basic Medicine, Jinan, Shandong Province, People's Republic of China.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00312-19. Print 2019 Oct.
In this study, we analyzed the global metabolomic changes associated with infection in mice in the presence or absence of sulfadiazine sodium (SDZ) treatment. BALB/c mice were infected with GT1 strain and treated orally with SDZ (250 μg/ml in water) for 12 consecutive days. Mice showed typical manifestations of illness at 20 days postinfection (dpi); by 30 dpi, 20% had survived and developed latent infection. We used ultraperformance liquid chromatography-mass spectrometry to profile the serum metabolomes in control (untreated and uninfected) mice, acutely infected mice, and SDZ-treated and infected mice. Infection induced significant perturbations in the metabolism of α-linolenic acid, purine, pyrimidine, arginine, tryptophan, valine, glycerophospholipids, and fatty acyls. However, treatment with SDZ seemed to alleviate the serum metabolic alterations caused by infection. The restoration of the serum metabolite levels in the treated mice was associated with better clinical outcomes. These data indicate that untargeted metabolomics can reveal biochemical pathways associated with restoration of the metabolic status of -infected mice following SDZ treatment and could be used to monitor responses to SDZ treatment. This study provides a new systems approach to elucidate the metabolic and therapeutic effects of SDZ in the context of murine toxoplasmosis.
在这项研究中，我们分析了感染与存在或不存在磺胺嘧啶钠（SDZ）治疗的情况下与感染相关的全球代谢组学变化。BALB/c 小鼠感染 GT1 株，并连续 12 天口服 SDZ（水中 250μg/ml）治疗。感染后 20 天，小鼠出现典型的疾病表现；到 30 天，20%的小鼠存活并发展为潜伏感染。我们使用超高效液相色谱-质谱法对对照（未处理和未感染）小鼠、急性感染小鼠以及 SDZ 处理和感染小鼠的血清代谢组进行了分析。感染诱导了 α-亚麻酸、嘌呤、嘧啶、精氨酸、色氨酸、缬氨酸、甘油磷脂和脂肪酸酰基的代谢显著紊乱。然而，SDZ 的治疗似乎减轻了感染引起的血清代谢改变。治疗小鼠的血清代谢物水平的恢复与更好的临床结果相关。这些数据表明，非靶向代谢组学可以揭示与 SDZ 治疗后感染小鼠代谢状态恢复相关的生化途径，并可用于监测对 SDZ 治疗的反应。这项研究为阐明 SDZ 在鼠弓形虫病中的代谢和治疗作用提供了一种新的系统方法。
