Combined effect of Thymus capitatus and Cinnamomum verum essential oils with conventional drugs against Candida albicans biofilm formation and elucidation of the molecular mechanism of action

Abstract

Biofilm formation by the pathogenic strain Candida albicans (C. albicans) is a crucial virulence factor on biotic and abiotic surfaces especially in medical devices. The present study investigated the effects of Cinnamomum verum and Thymus capitatus essential oils (EOs) and their combination with antifungal drugs on the development of biofilm and mature biofilm. The molecular mechanism of action was also investigated. Results showed that C. verum and T. capitatus EOs were broadly effective against C. albicans biofilm formation exhibiting 85.57% and 80.6% inhibition at half MIC values, respectively. Furthermore, they showed 92.79 and 94.46% eradication of C. albicans mature biofilm at 2xMIC values. Moreover, these EOs were able to reduce the production of secreted aspartic proteases by >90% at 0.75xMIC. The antibiofilm potency was improved when EOs were combined with AMB, effectively eradicating C. albicans mature biofilm on central venous catheter (CVC). Transcriptomic analyses indicated that EOs, especially when combined with AMB, down-regulate Ras-cAMP-Efg and MAPK signaling genes. In addition, EOs and their combination with AMB significantly inhibited the expression of adhesion and secreted aspartyl proteinase virulence factor genes. Our results demonstrated that C. verum and T. capitatus EOs and their combination with AMB could provide an effective treatment against C. albicans biofilm on medical devices.