Artemisinin May Disrupt Hyphae Formation by Suppressing Biofilm-Related Genes of Candida albicans : In Vitro and In Silico Approaches

• Published in: Antibiotics (Basel) 2024-03, Vol.13 (4), p.310
• Main Authors: Sumlu, Esra, Aydin, Merve, Korucu, Emine Nedime, Alyar, Saliha, Nsangou, Ahmed Moustapha
• Format: Article
• Language: English
• Subjects: Adhesion; Amino acids; Antifungal activity; Antiparasitic agents; Artemisinin; biofilm-related genes; Biofilms; Candida; Candida albicans; Drug dosages; Effectiveness; Extracellular matrix; FESEM; Fluconazole; Fungicides; Gene expression; Genes; Hydrogen bonds; Hyphae; Impact analysis; Infections; Kinases; Malaria; Molecular docking; Molecular interactions; Protein kinase A; Proteins; Toxicity; Virulence
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics13040310

This study aimed to assess the antifungal and antibiofilm efficacy of artemisinin against species, analyze its impact on gene expression levels within biofilms, and investigate the molecular interactions through molecular docking. The antifungal efficacy of artemisinin on a variety of species, including fluconazole-resistant and -susceptible species, was evaluated by the microdilution method. The effect of artemisinin on biofilm formation was investigated by MTT and FESEM. The mRNA expression of the genes related to biofilm was analyzed by qRT-PCR. In addition, molecular docking analysis was used to understand the interaction between artemisinin and at the molecular level with RAS1-cAMP-EFG1 and EFG1-regulated genes. Artemisinin showed higher sensitivity against non-albicans strains. Furthermore, artemisinin was strongly inhibitory against biofilms at 640 µg/mL. Artemisinin downregulated adhesion-related genes ALS3, HWP1, and ECE1, hyphal development genes UME6 and HGC1, and hyphal CAMP-dependent protein kinase regulators CYR1, RAS1, and EFG1. Furthermore, molecular docking analysis revealed that artemisinin and EFG1 had the highest affinity, followed by UME6. FESEM analysis showed that the fluconazole- and artemisinin-treated groups exhibited a reduced hyphal network, unusual surface bulges, and the formation of pores on the cell surfaces. Our study suggests that artemisinin may have antifungal potential and showed a remarkable antibiofilm activity by significantly suppressing adhesion and hyphal development through interaction with key proteins involved in biofilm formation, such as EFG1.