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

Abstract

Chong Pang,1,2 Jianshuang Chen,1,2 Lan Yang,3 Yang Yang,1 Haihua Qi,4 Ran Li,1 Yingying Cao,5 Hao Miao1 1School of Basic Medicine, Chengde Medical University, Chengde, Hebei, People’s Republic of China; 2Hebei Key Laboratory of Nerve Injury and Repair, Chengde, Hebei, People’s Republic of China; 3Hebei Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical University, Chengde, Hebei, People’s Republic of China; 4Department of Dermatology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People’s Republic of China; 5Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Hao Miao, School of Basic Medicine, Chengde Medical University, Chengde, Hebei, People’s Republic of China, Email [email protected] Yingying Cao, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Email [email protected]: 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.Keywords: shikonin, Ras1-cAMP-Efg1 signalling pathway, Candida albicans, biofilms

Keywords

• shikonin
• ras1-camp-efg1 signalling pathway
• candida albicans
• biofilms