Glycolipidomics of Liver Flukes and Host Tissues during Fascioliasis: Insights from Mass Spectrometry Imaging.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL ACS Infectious Diseases Pub Date : 2024-12-13 Epub Date: 2024-11-07 DOI:10.1021/acsinfecdis.4c00551
David Luh, Parviz Ghezellou, Sven Heiles, Svenja Gramberg, Simone Haeberlein, Bernhard Spengler
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Abstract

Fascioliasis, a zoonotic disease caused by liver flukes of the genus Fasciola, poses significant health threats to both humans and livestock. While some infections remain asymptomatic, others can lead to fatal outcomes, particularly during the acute phase characterized by the migration of immature parasites causing severe liver damage. Through the combination of data acquired via high-spatial-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) and nanohydrophilic interaction chromatography tandem mass spectrometry, we investigated glycosphingolipids (GSLs) in both adult and immature parasite stages as well as the host liver and bile duct to unravel the intricacies of the host-pathogen interplay and associated pathology. Several GSLs showed characteristic distribution patterns within the parasite depending on the fatty acid composition of their ceramides, notably including GSLs carrying very long-chain fatty acids. Additionally, GSL compositions within the tegument of immature versus adult parasites varied, suggestive of tissue remodeling upon maturation. AP-SMALDI MSI further enabled the identification of GSLs potentially involved in in vivo interactions between the host and immature parasites. Moreover, our experiments unveiled alterations in other lipid classes during Fasciola infection, providing a broader understanding of lipidomic changes associated with the disease. Collectively, our findings contribute to a deeper comprehension of the molecular intricacies underlying fascioliasis, with a specific focus on GSLs.

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法氏囊病期间肝吸虫和宿主组织的糖脂组学:质谱成像的启示。
法氏囊病是一种由法氏囊属肝吸虫引起的人畜共患疾病,对人类和牲畜的健康都构成严重威胁。虽然有些感染无症状,但有些感染可导致致命后果,尤其是在急性期,其特点是未成熟寄生虫的迁移导致严重的肝损伤。通过结合高空间分辨率大气压扫描微探针基质辅助激光解吸/电离质谱成像(AP-SMALDI MSI)和纳米亲水相互作用色谱串联质谱获得的数据,我们研究了成虫和未成熟寄生虫阶段以及宿主肝脏和胆管中的糖磷脂(GSLs),以揭示宿主-病原体相互作用和相关病理的复杂性。根据神经酰胺的脂肪酸组成,几种GSL在寄生虫体内呈现出特征性的分布模式,其中主要包括携带超长链脂肪酸的GSL。此外,未成年寄生虫和成年寄生虫的外壳内的 GSL 成分也各不相同,这表明寄生虫成熟后组织会发生重塑。AP-SMALDI MSI进一步鉴定了可能参与宿主与未成熟寄生虫体内相互作用的GSL。此外,我们的实验还揭示了法氏囊虫感染过程中其他脂质类别的变化,从而更广泛地了解了与该疾病相关的脂质体变化。总之,我们的研究结果有助于更深入地理解法氏囊病背后错综复杂的分子机制,特别是对GSL的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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