Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, 630 003, Tamil Nadu, India.
Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, 630 003, Tamil Nadu, India.
Biomed Pharmacother. 2021 Jan;133:111043. doi: 10.1016/j.biopha.2020.111043. Epub 2020 Dec 1.
Nosocomial Candida colonization causes Systemic candidiasis in human with invasive infections in immunocompromised patients. Of all Candida spp., C. albicans is dominant in morbidity of all systemic candidiasis but C. tropicalis is phenomenal in mortality, virulence aspects and resistance development against antifungal drugs. The present study investigated the synergistic anti-virulent activity of myristic acid (MA) and palmitic acid (PA) against insidious dimorphic Candida spp. (C. albicans and C. tropicalis). In vitro and qPCR results revealed the mechanisms of MA-PA combination effectively inhibiting various virulence aspects such as biofilm, hyphal formation, secreted aspartyl proteases, lipases, ergosterol biosynthesis and drug effluxes. Further, in Danio rerio (Zebrafish), the MA-PA treatment increased the survival of animals and also the treated groups showed decreased level of fungal burden compared to the infected controls, after 3 day of post infection. Histopathology of vital organs and SEM analysis of skin revealed a drastic recovery and reduced the inflammation of both Candida spp. infections in MA-PA treated animals. In addition, MA-PA treatment reduced the haemolysin and increased the susceptibility of Candida spp. in human blood model. Hence, this study suggested the therapeutic utilization of MA-PA as synergistic combination for their anti-inflammatory potency against systemic candidiasis and candidemia.
医院内念珠菌定植会导致免疫功能低下患者发生侵袭性感染,从而引发全身性念珠菌病。在所有念珠菌属中,白念珠菌在所有系统性念珠菌病的发病率中占主导地位,但热带念珠菌在死亡率、毒力和抗真菌药物耐药性方面表现出色。本研究调查了肉豆蔻酸(MA)和棕榈酸(PA)对隐匿性二相性念珠菌属(白念珠菌和热带念珠菌)协同抗毒力活性。体外和 qPCR 结果表明,MA-PA 联合有效地抑制了各种毒力方面,如生物膜、菌丝形成、分泌天冬氨酸蛋白酶、脂肪酶、麦角固醇生物合成和药物外排。此外,在斑马鱼(斑马鱼)中,MA-PA 处理增加了动物的存活率,并且与感染对照组相比,在感染后 3 天,治疗组的真菌负荷水平也降低。重要器官的组织病理学和皮肤的 SEM 分析显示,MA-PA 处理的动物的恢复情况明显好转,炎症反应减轻,念珠菌属感染得到缓解。此外,MA-PA 处理降低了溶血性和增加了人血模型中念珠菌属的敏感性。因此,本研究表明,MA-PA 作为协同组合具有治疗应用潜力,可用于治疗全身性念珠菌病和念珠菌血症的抗炎作用。