Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, Brazil.
Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-000, Brazil.
Molecules. 2020 Dec 5;25(23):5741. doi: 10.3390/molecules25235741.
The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of , the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC) of 25 µM for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite's morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.
双十八烷基二甲基溴化铵（DODAB）是一种双链阳离子脂质，具有很强的杀菌和抑菌活性；然而，其对原生动物寄生虫的毒性尚不清楚。在这里，我们展示了 DODAB 纳米尺寸阳离子双层片段对引起皮肤利什曼病的 的静止期前鞭毛体和无鞭毛体的抗利什曼原虫活性。在用 DODAB 处理后，我们分析了寄生虫表面 ζ-电位、寄生虫活力、细胞结构修饰和细胞内增殖。DODAB 的细胞毒性作用呈剂量依赖性，对两种生活阶段的中效浓度（EC）均为 25µM，与报道的细菌和真菌数据相当。DODAB 处理将膜 ζ-电位从负变为正，破坏寄生虫的形态，影响细胞大小调节，导致细胞内细胞器丢失，并可能在不破坏膜的情况下使质膜通透性失调。此外，治疗后存活的寄生虫诱导小寄生空泡，并且无法在巨噬细胞内增殖。总之，DODAB 表现出抗利什曼原虫活性，但其对原生动物膜的作用方式仍有待阐明。了解这种机制可以为开发新的寄生虫控制策略提供思路。
