Background

Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood.

Methods

In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA).

Results

We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase.

Conclusions

We have identified candidate marker metabolites that may be of relevance in the context of human malaria.

中文翻译：

---

通过高分辨率代谢组学分析感染疟疾寄生虫的小鼠的代谢变化

背景

疟疾感染可导致从无症状到严重的不同临床结果。宿主的病理生理变化和分子变化之间的关联，以及它们与疟疾进展严重程度的相关性尚不完全清楚。

方法

在这项研究中，我们讨论了基于质谱法对感染伯氏疟原虫（ANKA 株）的小鼠血清代谢物水平进行的时间分析。

结果

我们展示了全局扰动并确定了与疾病进展相关的特定代谢物的变化。虽然代谢组范围的变化在晚期疟疾中很明显，但一部分代谢物表现出与疾病进展高度相关的变化。这些代谢物在感染后早期发生变化，并在小鼠患上严重疾病时继续或维持这种变化。其中一些有可能成为严重疟疾的哨兵代谢物。此外，糖酵解代谢物、嘌呤核苷酸前体、色氨酸及其生物活性衍生物在晚期疾病中减少了许多倍。有趣的是，据报道，尿酸是一种代谢废物，在严重的人类疟疾中升高，随着疾病的进展而增加，随后似乎被解毒为尿囊素。

结论

我们已经确定了可能与人类疟疾相关的候选标记代谢物。