Department of Biological Sciences, School of Science and Technology, Sunway University, 47500, Subang Jaya, Selangor, Malaysia.
HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Parasitol Res. 2019 Jul;118(7):2295-2304. doi: 10.1007/s00436-019-06329-3. Epub 2019 May 15.
Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 μM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 μM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.
棘阿米巴属 T4 基因型是一种机会性病原体,与致盲性眼角膜炎和罕见但致命的中枢神经系统感染有关。由于棘阿米巴能够转化为具有耐药性、坚韧的壳保护的囊泡形式,从而导致感染复发,因此在抗微生物化学疗法中构成严重挑战。已知棘阿米巴滋养体的脂肪酸组成以油酸最为丰富,油酸在化学上是一种不饱和顺式 9-十八烷酸,天然存在于动物和植物油中。本研究旨在评估油酸对滋养体、囊泡以及寄生虫介导的宿主细胞细胞毒性的抗棘阿米巴作用。此外,还合成了油酸偶联的银纳米颗粒(AgNPs)并对其进行了测试。油酸-AgNPs 通过化学还原法合成,并通过紫外可见分光光度法、原子力显微镜、动态光散射分析和傅里叶变换红外光谱进行了表征。使用 10 和 5 μM 浓度的油酸单独和油酸偶联的 AgNPs 进行了活力、生长抑制、囊化和出囊实验。生物测定显示,油酸单独和油酸偶联的 AgNPs 均表现出显著的抗阿米巴作用,而纳米颗粒偶联进一步增强了油酸的功效。表型分化实验还表明,在 5 μM 时,囊化和出囊也受到显著抑制。此外,油酸和油酸偶联的 AgNPs 还抑制了由溶组织内阿米巴介导的宿主细胞细胞毒性,这是通过乳酸脱氢酶释放来确定的。这些发现首次表明,油酸偶联的 AgNPs 具有抗棘阿米巴活性,可能对治疗棘阿米巴属有应用潜力。