Cryptococcus neoformans is a yeast that mainly affects immunocompromised individuals and causes meningoencephalitis depending on the immune status of the host. The present study aimed to validate the efficacy of selective serotonin reuptake inhibitors, fluoxetine hydrochloride (FLH) and paroxetine hydrochloride (PAH), alone and in combination with amphotericin B (AmB) against C. neoformans. Susceptibility tests were conducted using the broth microdilution method and synergistic effects of combining FLH and PAH with AmB were analyzed using the checkerboard assay. Effects of minimum inhibitory concentration (MIC) and synergistic concentration were evaluated in biofilms by quantifying the biomass, measuring the viability by counting the colony-forming units (CFU/mL) and examining the size of the induced capsules. Cryptococcus neoformans was susceptible to FLH and PAH and the synergistic effect of FLH and PAH in combination with AmB reduced the MIC of AmB by up to 8-fold. The isolated substances and combination with AmB were able to reduce biofilm biomass and biofilm viability. In addition, FLH and PAH alone or in combination with AmB significantly decreased the size of the yeast capsules. Collectively, our results indicate the use of FLH and PAH as a promising prototype for the development of anti-cryptococcal drugs.

中文翻译：

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氟西汀和帕罗西汀联合两性霉素B对新型隐球菌的体外协同作用

新型隐球菌是一种酵母菌，主要影响免疫功能低下的个体并根据宿主的免疫状态引起脑膜脑炎。本研究旨在验证选择性 5-羟色胺再摄取抑制剂、盐酸氟西汀 (FLH) 和盐酸帕罗西汀 (PAH) 单独或与两性霉素 B (AmB) 联合使用对新型隐球菌的疗效。使用肉汤微量稀释法进行敏感性试验，并使用棋盘法分析 FLH 和 PAH 与 AmB 的协同效应。通过量化生物量、通过计数菌落形成单位 (CFU/mL) 和检查诱导胶囊的大小来评估生物膜中最小抑制浓度 (MIC) 和协同浓度的影响。新型隐球菌对 FLH 和 PAH 敏感，FLH 和 PAH 与 AmB 的协同作用使 AmB 的 MIC 降低了 8 倍。分离的物质和与 AmB 的组合能够降低生物膜生物量和生物膜活力。此外，FLH 和 PAH 单独或与 AmB 组合显着降低了酵母胶囊的大小。总的来说，我们的结果表明使用 FLH 和 PAH 作为开发抗隐球菌药物的有希望的原型。