Shikonin Inhibits Candida albicans Biofilms via the Ras1-cAMP-Efg1 Signalling Pathway

OBJECTIVE: To investigate the influence of shikonin (SK) on the formation of Candida albicans biofilms and discuss the possible mechanism. METHODS: The inhibition of the formation of C. albicans biofilms by SK was observed by scanning electron microscopy. A silicone film method and a water–hydrocarbon two-phase assay were performed to investigate the effects of SK on cell adhesion. Real-time reverse-transcription polymerase chain reaction was used to analyse the expression of genes related to cell adhesion and Ras1–cyclic adenosine monophosphate (cAMP) – enhanced filamentous growth protein 1 (Efg1) signalling pathway. Finally, the level of cAMP in C. albicans was detected and exogenous cAMP rescue experiment was conducted. RESULTS: The results showed that SK could destroy the typical three-dimensional structure of the biofilms, inhibit cell surface hydrophobicity and cell adhesion, downregulate the expression of Ras1-cAMP-Efg1 signalling pathway-related genes (ECE1, HWP1, ALS3, RAS1, CYR1, EFG1 and TEC1) and effectively reduce the production of key messenger cAMP in the Ras1-cAMP-Efg1 pathway. Meanwhile, exogenous cAMP reversed the inhibitory effect of SK on biofilms formation. CONCLUSION: Our results suggest that SK exhibits potential anti-C. albicans biofilms effects related to the inhibition of Ras1-cAMP-Efg1 pathway.