关键词: Acanthamoeba Ouabain PHMB Sodium P-Type ATPase

来  源:   DOI:10.1016/j.ijpddr.2024.100550   PDF(Pubmed)

Abstract:
Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.
摘要:
棘阿米巴,一个自由生活的变形虫,常见于各种自然环境中,比如河流和土壤,以及在公共浴场,游泳池,还有下水道.棘阿米巴可引起人类的严重疾病,如肉芽肿性阿米巴性脑炎和棘阿米巴性角膜炎(AK)。AK,最知名的疾病,可通过影响角膜导致永久性视力障碍或失明。AK通常会影响忽略适当清洁习惯的隐形眼镜佩戴者。AK的症状包括上皮和基质破坏,角膜浸润,和剧烈的眼部疼痛,偶尔需要手术切除整个眼球。目前的AK治疗涉及每小时施用含有聚六亚甲基杀生物剂(PHMB)的滴眼剂。然而,研究表明,它们对耐药菌株无效。棘阿米巴可以在不利的环境中形成囊肿作为生存机制,尽管确切的机制仍然未知。我们的实验表明,钠P型ATP酶(ACA1_065450)与包膜密切相关。此外,各种封闭缓冲区,如MgCl2或NaCl,诱导P型ATP酶的表达。此外,我们用了ouabain,ATPase抑制剂,抑制Na+/K+离子泵,因此降低了棘阿米巴的包封率。我们的主要目标是为AK开发一种先进的治疗方法。我们预计,乌巴因和PHMB的组合在未来可能会成为针对AK的有效治疗方法。
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