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

Chong Pang; Jianshuang Chen; Lan Yang; Yang Yang; Haihua Qi; Ran Li; Yingying Cao; Hao Miao

doi:10.2147/IJGM.S417327

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

Int J Gen Med. 2023 Jun 23:16:2653-2662. doi: 10.2147/IJGM.S417327. eCollection 2023.

Authors

Chong Pang^{1

2}, Jianshuang Chen^{1

2}, Lan Yang³, Yang Yang¹, Haihua Qi⁴, Ran Li¹, Yingying Cao⁵, Hao Miao¹

Affiliations

¹ School of Basic Medicine, Chengde Medical University, Chengde, Hebei, People's Republic of China.
² Hebei Key Laboratory of Nerve Injury and Repair, Chengde, Hebei, People's Republic of China.
³ Hebei Key Laboratory of Research and Development for Chinese Medicine, Chengde Medical University, Chengde, Hebei, People's Republic of China.
⁴ Department of Dermatology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People's Republic of China.
⁵ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.

Abstract

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.

Keywords: Candida albicans; Ras1-cAMP-Efg1 signalling pathway; biofilms; shikonin.

Grants and funding

This work was funded by Science and Technology Project of Hebei Education Department (QN2021004), 2021 Research Start-up Fund for High-level Talents of Chengde Medical University (202109) and Neurobiology Department of Chengde Medical University (071006).