Antivirulence Strategy against Candida albicans: Cumin Essential Oil Attenuates Virulence and Enhances Host Immune Defense.

Candida albicans is a deadly fungal pathogen, particularly in immunocompromised individuals, where a simple superficial infection rapidly transforms into life-threatening systemic candidiasis. Virulence factors of C. albicans include the yeast-to-hyphae transition, biofilm formation, and protease production, which are crucial for establishing infection. Targeting virulence factors is a promising strategy to combat C. albicans infections, which can overcome the limitations of conventional treatment modalities. Essential oils are important in this regard as they are used in traditional medicine due to their antimicrobial capabilities. This study is focused on the antivirulent activity of cumin essential oil (CEO), which significantly reduced the key virulence factors of C. albicans, such as germ tube formation and protease production. A subinhibitory concentration (0.015% v/v) of CEO downregulated the expression of the HWP1, ALS3, and RAS1 genes involved in regulating virulence. In silico studies demonstrated that major compounds of CEO interacted with key amino acid residues of secreted aspartyl proteases (Sap4, Sap5, Sap6) and heat shock protein (Hsp90), a regulator of hyphal formation. CEO significantly reduced biofilm formation of C. albicans in different simulated body fluids such as saliva, artificial urine, and tear fluid. Furthermore, CEO affected the host-pathogen interaction of C. albicans with THP-1 macrophages by increasing phagocytosis and inhibiting germ tube formation. Additionally, CEO treatment modulated the levels of pro-inflammatory and anti-inflammatory cytokines, suggesting that CEO also has immunomodulatory properties, in addition to its antivirulence activity. These results indicate that CEO could be a promising candidate for combating C. albicans infections.