Skaggs School of Pharmacy and Pharmaceutical Sciences, ‡Department of Computer Science, §Department of Pediatrics, ∥Center for Microbiome Innovation, and ⊥Collaborative Mass Spectrometry Innovation Center, University of California San Diego , La Jolla, California 92093, United States.
Anal Chem. 2017 Oct 3;89(19):10414-10421. doi: 10.1021/acs.analchem.7b02423. Epub 2017 Sep 22.
Trypanosoma cruzi parasites are the causative agents of Chagas disease, a leading infectious form of heart failure whose pathogenesis is still not fully characterized. In this work, we applied untargeted liquid chromatography-tandem mass spectrometry to heart sections from T. cruzi-infected and uninfected mice. We combined molecular networking and three-dimensional modeling to generate chemical cartographical heart models. This approach revealed for the first time preferential parasite localization to the base of the heart and regiospecific distributions of nucleoside derivatives and eicosanoids, which we correlated to tissue-damaging immune responses. We further detected novel cardiac chemical signatures related to the severity and ultimate outcome of the infection. These signatures included differential representation of higher- vs lower-molecular-weight carnitine and phosphatidylcholine family members in specific cardiac regions of mice infected with lethal or nonlethal T. cruzi strains and doses. Overall, this work provides new insights into Chagas disease pathogenesis and presents an analytical chemistry approach that can be broadly applied to the study of host-microbe interactions.
克氏锥虫寄生虫是恰加斯病的病原体，恰加斯病是一种主要的感染性心力衰竭形式，其发病机制尚未完全阐明。在这项工作中，我们应用非靶向液相色谱-串联质谱法对感染和未感染克氏锥虫的小鼠的心脏切片进行了分析。我们结合分子网络和三维建模生成了化学图谱心脏模型。这种方法首次揭示了寄生虫优先定位于心脏底部的位置，以及核苷衍生物和类二十烷酸的区域特异性分布，我们将这些分布与导致组织损伤的免疫反应相关联。我们还检测到与感染的严重程度和最终结果相关的新的心脏化学特征。这些特征包括在感染致死性或非致死性克氏锥虫菌株和剂量的小鼠的特定心脏区域中，较高和较低分子量肉碱和磷脂酰胆碱家族成员的差异表达。总的来说，这项工作为恰加斯病的发病机制提供了新的见解，并提出了一种分析化学方法，可广泛应用于宿主-微生物相互作用的研究。
