Proteomic analysis uncovers the modulation of ergosterol, sphingolipid and oxidative stress pathway by myristic acid impeding biofilm and virulence in Candida albicans.

ABSTRACT

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-1. 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.