Drug-Induced Lipid Remodeling in Leishmania Parasites.
Drug-Induced Lipid Remodeling in Leishmania Parasites.
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在利什曼原虫寄生虫中，药物诱导的脂质重塑。
DOI：
10.3390/microorganisms9040790
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发表时间：
2021-04-09
期刊：
影响因子：
4.5
通讯作者：
Karamysheva ZN
中科院分区：
文献类型：
--
作者：
Gutierrez Guarnizo SA;Tikhonova EB;Zabet-Moghaddam M;Zhang K;Muskus C;Karamyshev AL;Karamysheva ZN
利什曼原虫有效地对几种药物产生抗药性，包括历史上使用的主要抗利什曼药物锑。对锑的抗药性被认为是有效治疗利什曼病的主要危险因素。为了检测用于区分耐锑利什曼原虫菌株的生物标志物/生物模式，我们使用非靶向全球质谱仪来鉴定暴露锑前后敏感和耐药寄生虫中存在的细胞内脂质。脂肪体谱有效地区分了在锑压力下和不在锑压力下生长的敏感和抗性表型。耐药表型表现为磷脂酰胆碱显著下调、鞘磷脂降低、溶血磷脂酰胆碱升高，而敏感表型表现为长链脂肪酸甘油三酯上调和磷脂酰乙醇胺降低。我们的发现表明，抗锑寄生虫体内脂质成分的变化有助于对抗药物引起的氧化应激失衡的生理反应。我们已经确定了几种脂类作为与耐药性相关的潜在生物标记物。
Leishmania parasites efficiently develop resistance against several types of drugs including antimonials, the primary antileishmanial drug historically implemented. The resistance to antimonials is considered to be a major risk factor for effective leishmaniasis treatment. To detect biomarkers/biopatterns for the differentiation of antimony-resistant Leishmania strains, we employed untargeted global mass spectrometry to identify intracellular lipids present in antimony sensitive and resistant parasites before and after antimony exposure. The lipidomic profiles effectively differentiated the sensitive and resistant phenotypes growing with and without antimony pressure. Resistant phenotypes were characterized by significant downregulation of phosphatidylcholines, sphingolipid decrease, and lysophosphatidylcholine increase, while sensitive phenotypes were characterized by the upregulation of triglycerides with long-chain fatty acids and a tendency toward the phosphatidylethanolamine decrease. Our findings suggest that the changes in lipid composition in antimony-resistant parasites contribute to the physiological response conducted to combat the oxidative stress unbalance caused by the drug. We have identified several lipids as potential biomarkers associated with the drug resistance.
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影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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通讯作者：
Hotamisligil, Goekhan S.