Gonçalves-de-Albuquerque Cassiano Felippe, Cunha Carolina Medina Coeli da, Castro Léo Victor Grimaldi de, Martins Caroline de Azevedo, Barnese Marcos Roberto Colombo, Burth Patrícia, Younes-Ibrahim Mauricio
Laboratory of Immunopharmacology, Department of Physiology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20211-030, Brazil.
Neuroscience Graduate Program, Federal Fluminense University (UFF), Niteroi 24000-000, Brazil.
Microorganisms. 2023 Jun 29;11(7):1695. doi: 10.3390/microorganisms11071695.
Inada and Ido identified sp. as the pathogen responsible for Weil's Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism's interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated and purified, the complexity of the molecular interactions between these components and the host and the molecular mechanisms responsible for the systemic dysfunctions still needs to be fully unveiled. Leptospirosis affects virtually all animal species. Its cellular pathophysiology must involve a ubiquitous cellular mechanism in all eukaryotes. Na/K-ATPase is the molecular target of the leptospiral endotoxin (glycolipoprotein-GLP). Na/K-ATPase dysfunctions on different types of cells give rise to the organ disorders manifested in leptospirosis. Concomitantly, the development of a peculiar metabolic disorder characterized by dyslipidemia, with increased levels of circulating free fatty acids and an imbalance in the fatty acid/albumin molar ratio, triggers events of cellular lipotoxicity. Synergistically, multiple molecular stimuli are prompted during the infection, activating inflammasomes and Na/K-ATPase signalosome, leading to pro-inflammatory and metabolic alterations during leptospirosis. Leptospirosis involves diverse molecular mechanisms and alteration in patient inflammatory and metabolic status. Nonetheless, Na/K-ATPase is critical in the disease, and it is targeted by GLP, its components, and other molecules, such as fatty acids, that inhibit or trigger intracellular signaling through this enzyme. Herein, we overview the role of Na/K-ATPase during leptospirosis infection as a potential therapeutic target or an indicator of disease severity.
稻田和伊东在1915年确定了 菌为韦尔氏病的病原体。后来，证实钩端螺旋体可引起钩端螺旋体病。多年来，宿主微生物在细胞水平上的相互作用一直未被充分理解。尽管已经分离和纯化了不同的细菌成分，但这些成分与宿主之间分子相互作用的复杂性以及导致全身功能障碍的分子机制仍有待全面揭示。钩端螺旋体病几乎影响所有动物物种。其细胞病理生理学必定涉及所有真核生物中普遍存在的细胞机制。钠钾ATP酶是钩端螺旋体内毒素（糖脂蛋白-GLP）的分子靶点。不同类型细胞上的钠钾ATP酶功能障碍会导致钩端螺旋体病中出现的器官紊乱。与此同时，一种以血脂异常为特征的特殊代谢紊乱的发展，伴随着循环游离脂肪酸水平的升高以及脂肪酸/白蛋白摩尔比的失衡，引发细胞脂毒性事件。协同地，感染期间会引发多种分子刺激，激活炎性小体和钠钾ATP酶信号体，导致钩端螺旋体病期间的促炎和代谢改变。钩端螺旋体病涉及多种分子机制以及患者炎症和代谢状态的改变。尽管如此，钠钾ATP酶在该疾病中至关重要，它是GLP及其成分以及其他分子（如脂肪酸）的作用靶点，这些分子通过该酶抑制或触发细胞内信号传导。在此，我们概述钠钾ATP酶在钩端螺旋体病感染期间作为潜在治疗靶点或疾病严重程度指标的作用。
