Persistent biofluid small molecule alterations induced by Trypanosoma cruzi infection are not restored by antiparasitic treatment.
Persistent biofluid small molecule alterations induced by Trypanosoma cruzi infection are not restored by antiparasitic treatment.
复制标题
抗寄生虫治疗无法恢复由克氏锥虫感染引起的持续性生物流体小分子改变。
DOI：
10.1101/2023.06.03.543565
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Liu,
中科院分区：
文献类型：
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作者：
Dean,DanyaA;Roach,Jarrod;vonBargen,RebeccaUlrich;Xiong,Yi;Kane,ShelleyS;Klechka,London;Wheeler,Kate;Sandoval,MichaelJimenez;Lesani,Mahbobeh;Hossain,Ekram;Katemauswa,Mitchelle;Schaefer,Miranda;Harris,Morgan;Barron,Sayre;Liu,
恰加斯病（Chagas Disease， CD）是由克氏锥虫（T. cruzi）原虫引起的一种复杂的寄生虫病，在诊断感染和监测治疗成功方面缺乏医学措施。为了解决这一差距，我们通过液相色谱串联质谱分析临床可获得的生物流体：唾液、尿液和血浆，分析了克鲁兹锥虫感染小鼠代谢组的变化。在小鼠和寄生虫基因型中，尿液最能指示感染状态。尿中受感染影响的代谢物包括犬尿酸、酰基肉碱和苏氨基氨基腺苷。基于这些结果，我们试图将尿液作为评估CD治疗成功的工具。引人注目的是，发现在苯并硝唑抗寄生虫治疗后清除寄生虫的小鼠与未清除寄生虫的小鼠具有相当的总体尿液代谢组。这些结果与临床试验数据相吻合，其中苯并硝唑治疗并没有改善晚期疾病患者的预后。总的来说，这项研究提供了新的基于小分子的CD诊断方法和评估功能性治疗反应的新方法。
Chagas Disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromatography tandem mass spectrometry analysis of clinically-accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status, across mouse and parasite genotypes. Metabolites perturbed by infection in the urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had comparable overall urine metabolome to mice that failed to clear parasites. These results match with clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease. Overall, this study provides insights into new small molecule-based CD diagnostic methods and a new approach to assess functional treatment response.