Abstract
Candida albicans is a common fungal pathogen in humans. Biofilm formation is an important virulence factor of C. albicans infections. We investigated the ability of the plant-derived cannabidiol (CBD) to inhibit the formation and removal of fungal biofilms. Further, we evaluated its mode of action. Our findings demonstrate that CBD exerts pronounced time-dependent inhibitory effects on biofilm formation as well as disruption of mature biofilm at a concentration range below minimal inhibitory and fungicidal concentrations. CBD acts at several levels. It modifies the architecture of fungal biofilm by reducing its thickness and exopolysaccharide (EPS) production accompanied by downregulation of genes involved in EPS synthesis. It alters the fungal morphology that correlated with upregulation of yeast-associated genes and downregulation of hyphae-specific genes. Importantly, it represses the expression of C. albicans virulence-associated genes. In addition, CBD increases ROS production, reduces the intracellular ATP levels, induces mitochondrial membrane hyperpolarization, modifies the cell wall, and increases the plasma membrane permeability. In conclusion, we propose that CBD exerts its activity towards C. albicans biofilm through a multi-target mode of action, which differs from common antimycotic agents, and thus can be explored for further development as an alternative treatment against fungal infections.
Highlights
We initially studied the effect of CBD on biofilm formation
Since the fungal pathogenicity is mostly attributed to their capacity to adhere and to accumulate on various surfaces, the novel antifungal strategy should focus on the development of agents that prevent biofilm formation and eradicate existing biofilms
Our results clearly show strong dose- and time-dependent inhibition of C. albicans biofilm formation by the phytocannabinoid CBD
Summary
The fungus Candida albicans is a commensal microorganism found in various sites of the human body such as the oral cavity, vagina, and the lungs. It is the most common fungal pathogen in humans, often associated with serious invasive mucosal and systemic infections. One of the most important virulence properties of C. albicans is attributed to biofilm formation on either biotic or abiotic surfaces [1,2,3,4]. Formation of biofilm is a complex process that involves attachment to the surface, colonization, and maturation. Biofilms consist of highly structured multilayer network of various cell types: yeast-form cells, pseudohyphal cells, and hyphal cells enwrapped in a protective extracellular matrix [5,6,7,8]
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