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Abstract：
Candida species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six N-substituted phthalimides against three Candida species. Of the derivatives, N-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive Candida albicans and Candida parapsilosis. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio parahaemolyticus, along with the polymicrobial biofilms of S. epidermidis and C. albicans. NBP markedly inhibited the hyphal formation and cell aggregation of C. albicans and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., ECE1, HWP1, and UME6, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various Candida strains.
摘要：
念珠菌属包括引起念珠菌病的普遍存在的致病性真菌属。它们是人类几种粘膜和全身性感染的主要病因之一，可以在各种环境中生存。在这项研究中,我们调查了抗真菌药,抗生物膜，6种N-取代邻苯二甲酰亚胺对3种念珠菌的抗菌丝作用。在衍生物中，正丁基邻苯二甲酰亚胺(NBP)是最有效的，最小抑制浓度（MIC）为100µg/ml，并且在氟康唑耐药和氟康唑敏感的白色念珠菌和近apsilia念珠菌中均以剂量依赖性抑制亚抑制浓度（10-50µg/ml）的生物膜。NBP还有效抑制了其他病原体包括尿路致病性大肠杆菌的生物膜形成，表皮葡萄球菌，金黄色葡萄球菌,和副溶血性弧菌,以及表皮葡萄球菌和白色念珠菌的多微生物生物膜。NBP显著抑制白色念珠菌菌丝形成和细胞聚集,并以剂量依赖性方式改变其集落形态。基因表达分析表明，NBP显著下调重要的hyphl和生物膜相关基因的表达，即，ECE1、HWP1和UME6治疗后。在线虫模型中，NBP在2至20µg/ml的浓度范围内也表现出轻度毒性。因此,这项研究表明，NBP对各种念珠菌菌株具有抗生物膜和抗真菌潜力。
