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胃肠道线虫感染阶段的代谢组和脂质组,以及…… (原文此处不完整,翻译可能存在一定局限性)

Metabolomes and Lipidomes of the Infective Stages of the Gastrointestinal nematodes, and .

作者信息

Yeshi Karma, Creek Darren J, Anderson Dovile, Ritmejerytė Edita, Becker Luke, Loukas Alex, Wangchuk Phurpa

机构信息

Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Building E4, McGregor Rd, Smithfield, Cairns, QLD 4878, Australia.

Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.

出版信息

Metabolites. 2020 Nov 6;10(11):446. doi: 10.3390/metabo10110446.

Abstract

Soil-transmitted helminths, including hookworms and whipworms, infect billions of people worldwide. Their capacity to penetrate and migrate through their hosts' tissues is influenced by the suite of molecules produced by the infective developmental stages. To facilitate a better understanding of the immunobiology and pathogenicity of human hookworms and whipworms, we investigated the metabolomes of the infective stage of third-stage larvae (L3) which penetrate the skin and eggs which are orally ingested, using untargeted liquid chromatography-mass spectrometry (LC-MS). We identified 55 polar metabolites through Metabolomics Standard Initiative level-1 (MSI-I) identification from and infective stages, out of which seven were unique to excretory/secretory products (ESPs) of L3. Amino acids were a principal constituent (33 amino acids). Additionally, we identified 350 putative lipids, out of which 28 (all known lipids) were unique to N. brasiliensis L3 somatic extract and four to embryonated egg somatic extract. Glycerophospholipids and glycerolipids were the major lipid groups. The catalogue of metabolites identified in this study shed light on the biology, and possible therapeutic and diagnostic targets for the treatment of these critical infectious pathogens. Moreover, with the growing body of literature on the therapeutic utility of helminth ESPs for treating inflammatory diseases, a role for metabolites is likely but has received little attention thus far.

摘要

土壤传播的蠕虫,包括钩虫和鞭虫,感染了全球数十亿人。它们穿透并在宿主组织中迁移的能力受感染性发育阶段产生的一系列分子的影响。为了更好地理解人类钩虫和鞭虫的免疫生物学及致病性,我们使用非靶向液相色谱-质谱联用技术(LC-MS),研究了穿透皮肤的第三期幼虫(L3)感染阶段以及经口摄入的虫卵的代谢组。我们通过代谢组学标准倡议一级(MSI-I)鉴定,从巴西钩虫和十二指肠钩虫的感染阶段中鉴定出55种极性代谢物,其中7种是巴西钩虫L3排泄/分泌产物(ESPs)所特有的。氨基酸是主要成分(33种氨基酸)。此外,我们鉴定出350种推定脂质,其中28种(均为已知脂质)是巴西钩虫L3体细胞提取物所特有的,4种是受精虫卵体细胞提取物所特有的。甘油磷脂和甘油脂是主要的脂质类别。本研究中鉴定出的代谢物目录揭示了这些关键感染性病原体的生物学特性以及可能的治疗和诊断靶点。此外,随着关于蠕虫ESPs治疗炎症性疾病的治疗效用的文献不断增加,代谢物可能发挥作用,但迄今为止很少受到关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b964/7694664/a310b37f95ef/metabolites-10-00446-g001.jpg

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