Metabolite Biomarkers of Leishmania Antimony Resistance.
Metabolite Biomarkers of Leishmania Antimony Resistance.
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DOI：
10.3390/cells10051063
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发表时间：
2021-04-30
期刊：
影响因子：
6
通讯作者：
Muskus CE
中科院分区：
文献类型：
--
作者：
Gutierrez Guarnizo SA;Karamysheva ZN;Galeano E;Muskus CE
利什曼原虫引起的利什曼病是流行病学上最重要的被忽视的热带疾病之一。利什曼原虫表现出很高的耐药性，耐药性是公共卫生的主要威胁之一，因为它与发病率，死亡率和医疗费用增加有关。锑药物是历史上主要用于治疗利什曼病的药物。然而，尽管锑抗性已被广泛记录，但所涉及的机制尚未完全理解。在这项研究中，我们的目的是确定潜在的代谢物生物标志物的锑耐药性，可以改善利什曼病的治疗。这里，使用L.的tropica promastigotes作为生物模型，我们表明，锑的反应水平可以潜在地预测使用1H-NMR为基础的代谢组学分析。抗锑寄生虫在细胞内和细胞外水平的代谢物组成的差异，这表明需要代谢重塑来对抗药物。简单省时的外代谢组学分析可以有效地用于区分敏感和耐药寄生虫。我们的研究结果表明，代谢物组成的变化与优化的反应，渗透/氧化应激和碳能量代谢的重排。能量代谢的激活与抗氧化应激反应期间的高能量需求有关。同时发现脯氨酸、乳酸等代谢产物的变化与抗锑水平呈线性关系，与疟原虫的抗药性有密切关系。一个潜在的代谢物生物标志物的列表进行了描述和讨论。
Leishmania parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. Leishmania exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using L. tropica promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using 1H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite’s efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.
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影响因子：
4.9
作者：
Berg, Maya;Garcia-Hernandez, Raquel;Gamarro, Francisco
通讯作者：
Gamarro, Francisco
影响因子：
3.5
作者：
dos Santos Ferreira, Claudio;Monteiro de Castro Pimenta, Adriano;Frezard, Frederic
通讯作者：
Frezard, Frederic
影响因子：
3.4
作者：
Frezard, Frederic;Silva, Heveline;Demicheli, Cynthia
通讯作者：
Demicheli, Cynthia
在利什曼原虫寄生虫中，药物诱导的脂质重塑。
影响因子：
4.5
作者：
Gutierrez Guarnizo SA;Tikhonova EB;Zabet-Moghaddam M;Zhang K;Muskus C;Karamyshev AL;Karamysheva ZN
通讯作者：
Karamysheva ZN
影响因子：
2.9
作者：
Canuto, Gisele A. B.;Castilho-Martins, Emerson A.;Barbas, Coral
通讯作者：
Barbas, Coral