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咖啡因和齐墩果酸通过诱导棘阿米巴程序性细胞死亡发挥杀阿米巴活性

Amoebicidal Activity of Caffeine and Maslinic Acid by the Induction of Programmed Cell Death in Acanthamoeba.

作者信息

Martín-Navarro Carmen M, López-Arencibia Atteneri, Sifaoui Ines, Reyes-Batlle María, Fouque Emilie, Osuna Antonio, Valladares Basilio, Piñero José E, Héchard Yann, Maciver Sutherland K, Lorenzo-Morales Jacob

机构信息

University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.

Microbiologie de l'eau, Laboratoire Ecologie et Biologie des Interactions, UMR CNRS 7267, Université de Poitiers, Poitiers, France.

出版信息

Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.02660-16. Print 2017 Jun.

Abstract

Free-living amoebae of the genus are the causal agents of a sight-threatening ulceration of the cornea called keratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of infections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, treatments should target both the trophozoite and the cyst stages, as cysts are known to confer resistance to treatment. In this study, we document the activities of caffeine and maslinic acid against both the trophozoite and the cyst stages of three clinical strains of These drugs were chosen because they are reported to inhibit glycogen phosphorylase, which is required for encystation. Maslinic acid is also reported to be an inhibitor of extracellular proteases, which may be relevant since the protease activities of species are correlated with their pathogenicity. We also provide evidence for the first time that both drugs exert their anti-amoebal effects through programmed cell death.

摘要

属的自由生活阿米巴是一种称为角膜炎的威胁视力的角膜溃疡的病原体,也是罕见但通常致命的疾病肉芽肿性阿米巴脑炎的病原体。尽管有许多治疗感染的方法,但它们通常疗程长和/或疗效有限。为了获得最佳临床结果,治疗应针对滋养体和包囊阶段,因为已知包囊会导致治疗耐药。在本研究中,我们记录了咖啡因和山楂酸对三种临床分离株的滋养体和包囊阶段的活性。选择这些药物是因为据报道它们能抑制包囊形成所需的糖原磷酸化酶。据报道,山楂酸也是细胞外蛋白酶的抑制剂,这可能是相关的,因为该物种的蛋白酶活性与其致病性相关。我们还首次提供证据表明这两种药物都通过程序性细胞死亡发挥其抗阿米巴作用。

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