Abstract
Lichens, due to their symbiotic nature (association between fungi and algae), constitute a chemical factory of original compounds. Polyphenolic compounds (depsides and depsidones) are the main constituents of lichens and are exclusively biosynthesized by these organisms. A panel of 11 polyphenols was evaluated for their anti-biofilm activity against Candida albicans biofilms on the maturation phase (anti-maturation) (MMIC50) as well as on preformed 24-h-old biofilm (anti-biofilm) (MBIC50) using the XTT assay. Minimum inhibitory concentrations of compounds (MICs) against C. albicans planktonic yeast were also determined using a broth microdilution method. While none of the tested compounds were active against planktonic cells (IC50 > 100 µg/ml), three depsides slowed the biofilm maturation (MMIC50 ≤12.5 µg/ml after 48 h of contact with Candida cells). Evernic acid was able to both slow the maturation and reduce the already formed biofilms with MBIC50 ≤12.5 µg/ml after 48 h of contact with the biofilm. This compound shows a weak toxicity against HeLa cells (22%) at the minimal active concentration and no hemolytic activity at 100 µg/ml. Microscopic observations of evernic acid and optimization of its solubility were performed to further study this compound. This work confirmed the anti-biofilm potential of depsides, especially evernic acid, and allows to establish the structure–activity relationships to better explain the anti-biofilm potential of these compounds.
Highlights
Candida albicans is a common microorganism which colonizes the gastrointestinal and reproductive tracts and oral cavity of humans (Underhill and Iliev, 2014; Nobile and Johnson, 2015)
Compounds 1–3 were chosen following a preliminary study which screened the activity of 38 lichen species and revealed large amounts of these depsides in the lichen extracts displaying the most promising anti-biofilm activities (Millot et al, 2017)
The capacity of the studied compounds to limit biofilm growth and maturation just after the C. albicans adhesion phase was evaluated in order to identify molecules that could prevent C. albicans colonization of surfaces
Summary
Candida albicans is a common microorganism which colonizes the gastrointestinal and reproductive tracts and oral cavity of humans (Underhill and Iliev, 2014; Nobile and Johnson, 2015). Lichen Depsides Targeting Candida Biofilms et al, 2015). In these cases, Candida biofilms may occur on catheter, dental, and/or mucosal surfaces. The first step for the colonization and biofilm formation is the adherence of Candida yeasts onto the host surfaces (Radford et al, 1999; Soustre, 2004; Bürgers et al, 2010). Biofilm formation is implicated in 80% of infections and is an important virulence factor. Biofilms are specially resistant to convential antifungal drugs, and the therapeutic options are limited. The development of new drugs is crucial to enrich the list of anti-Candida drugs active against biofilms, which is currently limited to the lipid formulation of amphotericin B and echinocandins
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