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结核病会导致人类患者、感染分枝杆菌的小鼠和斑马鱼幼虫发生高度保守的代谢变化。

Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria-infected mice and zebrafish larvae.

机构信息

Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands.

Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.

出版信息

Sci Rep. 2020 Jul 15;10(1):11635. doi: 10.1038/s41598-020-68443-y.

DOI:10.1038/s41598-020-68443-y
PMID:32669636
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7363909/
Abstract

Tuberculosis is a highly infectious and potentially fatal disease accompanied by wasting symptoms, which cause severe metabolic changes in infected people. In this study we have compared the effect of mycobacteria infection on the level of metabolites in blood of humans and mice and whole zebrafish larvae using one highly standardized mass spectrometry pipeline, ensuring technical comparability of the results. Quantification of a range of circulating small amines showed that the levels of the majority of these compounds were significantly decreased in all three groups of infected organisms. Ten of these metabolites were common between the three different organisms comprising: methionine, asparagine, cysteine, threonine, serine, tryptophan, leucine, citrulline, ethanolamine and phenylalanine. The metabolomic changes of zebrafish larvae after infection were confirmed by nuclear magnetic resonance spectroscopy. Our study identified common biomarkers for tuberculosis disease in humans, mice and zebrafish, showing across species conservation of metabolic reprogramming processes as a result of disease. Apparently, the mechanisms underlying these processes are independent of environmental, developmental and vertebrate evolutionary factors. The zebrafish larval model is highly suited to further investigate the mechanism of metabolic reprogramming and the connection with wasting syndrome due to infection by mycobacteria.

摘要

结核病是一种高度传染性且可能致命的疾病，伴有消瘦症状，导致感染者发生严重的代谢变化。在这项研究中，我们使用一种高度标准化的质谱分析流程，比较了分枝杆菌感染对人类和小鼠血液以及整个斑马鱼幼虫中代谢物水平的影响，确保了结果的技术可比性。对一系列循环小胺的定量分析表明，大多数这些化合物的水平在所有三种感染生物中都显著降低。这十种代谢物在三种不同的生物中是共有的：蛋氨酸、天冬酰胺、半胱氨酸、苏氨酸、丝氨酸、色氨酸、亮氨酸、瓜氨酸、乙醇胺和苯丙氨酸。感染后斑马鱼幼虫的代谢组学变化通过核磁共振波谱法得到了证实。我们的研究在人类、小鼠和斑马鱼中确定了结核病的共同生物标志物，表明疾病导致代谢重编程过程在物种间具有保守性。显然，这些过程的机制独立于环境、发育和脊椎动物进化因素。斑马鱼幼虫模型非常适合进一步研究由于分枝杆菌感染导致的代谢重编程机制及其与消瘦综合征的联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/81d05a843b31/41598_2020_68443_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/81d05a843b31/41598_2020_68443_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/70c0321767a0/41598_2020_68443_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/9a56c715830a/41598_2020_68443_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/896ec949b671/41598_2020_68443_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/22e39c02c329/41598_2020_68443_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4567/7363909/81d05a843b31/41598_2020_68443_Fig7_HTML.jpg

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