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.
J Proteomics. 2019 Sep 30;208:103503. doi: 10.1016/j.jprot.2019.103503. Epub 2019 Aug 24.
Candida albicans, a dimorphic opportunistic fungus is known to form robust biofilm and commonly associated with superficial and life threatening systemic infections. The repertoire of C. albicans infection is comprehensive due to its biofilm mediated virulence and occurrence of resistance against conventional antifungal drugs. Natural bioactive compounds are known for their antivirulence potency against fungi circumventing their resistance. In the present study, antibiofilm and antihyphal efficacies of myristic acid (MA), a major component of Myristica fragrans against C. albicans was assessed. Results of biofilm assays, optical microscopic analyses showed the potent inhibition of biofilm and hyphal formation by MA at 125 μg mL. Proteomic analysis revealed the ability of MA to target proteins involved in various virulence pathways such as ergosterol synthesis, sphingolipid metabolism, multidrug resistance and the oxidative stress. The results of gene expression analysis and biochemical assays validated the outcomes of proteomic analysis. This investigation emphasized the potent antibiofilm and virulence inhibitory potentials of MA. Hence, MA could be clinically utilized to control infections caused by C. albicans. BIOLOGICAL SIGNIFICANCE: The conventional antifungal drugs acquire single target pattern by regulating either sterol synthesis or drug efflux pump in C. albicans that ushers drug-resistance. But Myristic acid attenuates C. albicans virulence by negative regulation of proteins involved in sterol synthesis & uptake, sphingolipids and antioxidant activity. In the current study, the multi-target efficacy and the ability to inhibit biofilm and hyphae mediated virulence factors without affecting the cellular metabolism of C. albicans marks myristic acid as a potent anti-candida agent against drug resistant Candida species.
白色念珠菌是一种二相性机会致病菌，能够形成坚固的生物膜，通常与浅表性和威胁生命的全身感染有关。由于其生物膜介导的毒力和对常规抗真菌药物的耐药性，白色念珠菌感染的范围很广。天然生物活性化合物因其抗真菌的毒力作用而闻名，能够规避真菌的耐药性。在本研究中，评估了肉豆蔻酸（MA）作为肉豆蔻的主要成分对白色念珠菌的抗生物膜和抗菌丝形成作用。生物膜分析结果和光学显微镜分析表明，MA 在 125μg/mL 时能有效抑制生物膜和菌丝形成。蛋白质组学分析显示，MA 能够靶向参与各种毒力途径的蛋白质，如麦角固醇合成、鞘脂代谢、多药耐药和氧化应激。基因表达分析和生化分析的结果验证了蛋白质组学分析的结果。这项研究强调了 MA 具有强大的抗生物膜和抑制毒力的潜力。因此，MA 可以在临床上用于控制白色念珠菌引起的感染。生物学意义：传统的抗真菌药物通过调节麦角固醇合成或药物外排泵在白色念珠菌中获得单一靶标模式，从而导致耐药性。但是，肉豆蔻酸通过负调控参与麦角固醇合成和摄取、鞘脂和抗氧化活性的蛋白质来减弱白色念珠菌的毒力。在目前的研究中，MA 具有多靶标功效，能够抑制生物膜和菌丝介导的毒力因子，而不影响白色念珠菌的细胞代谢，这使其成为一种针对耐药性白色念珠菌的有效抗真菌药物。
