Abstract
Candida albicans is an opportunistic pathogen and responsible for candidiasis. C. albicans readily forms biofilms on various biotic and abiotic surfaces, and these biofilms can cause local and systemic infections. C. albicans biofilms are more resistant than its free yeast to antifungal agents and less affected by host immune responses. Transition of yeast cells to hyphal cells is required for biofilm formation and is believed to be a crucial virulence factor. In this study, six components of ginger were investigated for antibiofilm and antivirulence activities against a fluconazole-resistant C. albicans strain. It was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm formation. In particular, 6-shogaol at 10 μg/ml significantly reduced C. albicans biofilm formation but had no effect on planktonic cell growth. Also, 6-gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free-living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol and 6-shogaol reduced C. albicans virulence in a nematode infection model without causing toxicity at the tested concentrations. Transcriptomic analysis using RNA-seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters (CDR1, CDR2, and RTA3), but repressed the expressions of several hypha/biofilm related genes (ECE1 and HWP1), which supported observed phenotypic changes. These results highlight the antibiofilm and antivirulence activities of the ginger components, 6-gingerol and 6-shogaol, against a drug resistant C. albicans strain.
Highlights
Candida albicans is an opportunistic pathogen normally present on skin and mucous membranes, such as, those of the vagina, mouth, and rectum
Yeast cells initially attach to a surface, and this is followed by germ tube formation and hyphal transition, and mature biofilms are typically formed within 24 h (Nobile et al, 2006b)
We investigated whether three gingerols (6-gingerol, 8-gingerol, and 10-gingerol) and three shogaols (6-shogaol, 8shogaol, and 10-shogaol) affect biofilm formation by fluconazoleresistant C. albicans DAY185, cell growth was measured in the presence of these agents
Summary
Candida albicans is an opportunistic pathogen normally present on skin and mucous membranes, such as, those of the vagina, mouth, and rectum. C. albicans colonizes host tissues and various indwelling medical devices (Ramage et al, 2005; Sardi et al, 2013) and readily develops biofilms on biotic and abiotic surfaces that are intrinsically resistant to conventional antifungal therapeutics and the host immune system (Nobile et al, 2006b). Yeast cells initially attach to a surface, and this is followed by germ tube formation and hyphal transition, and mature biofilms are typically formed within 24 h (Nobile et al, 2006b). Antivirulence Activities of 6-Gingerol and 6-Shogaol appears to regulate biofilm maturation, and hyphal transition is considered a crucial virulence factor in Candida infections (Carradori et al, 2016). Novel antivirulence drugs not prone to the development of antifungal resistance, are required to eradicate C. albicans biofilms and virulence
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