Chemical Cartography Approaches to Study Trypanosomatid Infection.
Chemical Cartography Approaches to Study Trypanosomatid Infection.
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DOI：
10.3791/63255
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发表时间：
2022-01-21
期刊：
影响因子：
--
通讯作者：
McCall LI
中科院分区：
文献类型：
--
作者：
Dean DA;Haffner JJ;Katemauswa M;McCall LI
病原体趋向性和疾病趋向性是指病原体选择性地定植或损害的组织部位，从而导致局部疾病症状。感染人类的锥虫类寄生虫包括克氏锥虫，它是恰加斯病的病原体；布氏锥虫，它是昏睡病的病原体；以及利什曼原虫属，是利什曼病的病原体。它们总共影响全球2000万人。这些寄生虫表现出特定的趋向性：克氏锥虫趋向心脏、食管、结肠，布氏锥虫趋向脂肪组织、胰腺、皮肤、循环系统和中枢神经系统，亲皮肤的利什曼原虫菌株趋向皮肤，亲内脏的利什曼原虫菌株趋向肝脏、脾脏和骨髓。因此，从空间角度理解锥虫病的发病机制至关重要。化学制图通过液相色谱 - 质谱法生成小分子丰度的三维可视化图像，并与微生物学和免疫学参数进行比较。本方案展示了如何将化学制图应用于研究锥虫感染期间的致病过程，从系统的组织取样和代谢物提取开始，接着是液相色谱 - 串联质谱数据采集，最后生成代谢物分布的三维图谱。这种方法可用于多个研究问题，例如克氏锥虫、布氏锥虫或利什曼原虫在组织定植的营养需求、感染部位的免疫代谢以及局部组织代谢紊乱与临床疾病症状之间的关系，从而全面深入了解锥虫病的发病机制。
Pathogen tropism and disease tropism refer to the tissue locations selectively colonized or damaged by pathogens, leading to localized disease symptoms. Human-infective trypanosomatid parasites include Trypanosoma cruzi, the causative agent of Chagas disease; Trypanosoma brucei, the causative agent of sleeping sickness; and Leishmania species, causative agents of leishmaniasis. Jointly, they affect 20 million people across the globe. These parasites show specific tropism: heart, esophagus, colon for T. cruzi, adipose tissue, pancreas, skin, circulatory system and central nervous system for T. brucei, skin for dermotropic Leishmania strains, and liver, spleen, and bone marrow for viscerotropic Leishmania strains. A spatial perspective is therefore essential to understand trypanosomatid disease pathogenesis. Chemical cartography generates 3D visualizations of small molecule abundance generated via liquid chromatography-mass spectrometry, in comparison to microbiological and immunological parameters. This protocol demonstrates how chemical cartography can be applied to study pathogenic processes during trypanosomatid infection, beginning from systematic tissue sampling and metabolite extraction, followed by liquid chromatography-tandem mass spectrometry data acquisition, and concluding with the generation of 3D maps of metabolite distribution. This method can be used for multiple research questions, such as nutrient requirements for tissue colonization by T. cruzi, T. brucei, or Leishmania, immunometabolism at sites of infection, and the relationship between local tissue metabolic perturbation and clinical disease symptoms, leading to comprehensive insight into trypanosomatid disease pathogenesis.
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影响因子：
5.3
作者：
Hoffman K;Liu Z;Hossain E;Bottazzi ME;Hotez PJ;Jones KM;McCall LI
通讯作者：
McCall LI
影响因子：
16.6
作者：
Lu W;Su X;Klein MS;Lewis IA;Fiehn O;Rabinowitz JD
通讯作者：
Rabinowitz JD
DOI：
10.1073/pnas.1424409112
发表时间：
2015-04-28
影响因子：
11.1
作者：
Bouslimani, Amina;Porto, Carla;Dorrestein, Pieter C.
通讯作者：
Dorrestein, Pieter C.
影响因子：
3.4
作者：
Lewis, Michael D.;Francisco, Amanda Fortes;Kelly, John M.
通讯作者：
Kelly, John M.
DOI：
10.1016/j.jpba.2005.03.009
发表时间：
2005-09-01
影响因子：
3.4
作者：
Larger, PJ;Breda, M;James, CA
通讯作者：
James, CA