Efficacy of zosteric acid against Candida albicans biofilm

The ubiquitous commensal yeast Candida albicans is frequently implicated in many invasive biofilm-associated infections, exhibiting resistance to traditional antifungal agents. As a consequence, a new approach to controlling fungal biofilm has become imperative. One of the most recent and fascinating trends in antibiofilm strategies is the employment of molecules able to interfere, in sublethal doses, with the formation of biofilms. To this end, according to the literature the plant metabolite zosteric acid is potentially a good candidate as it combines low toxicity with antifouling properties. The aim of the present work was to test, for the first time, the efficacy of zosteric acid against Candida albicans biofilm. The promising non-toxic antifoulant was synthesized using a novel method and the most effective concentration was obtained from microplate assays using a mathematical representation able to simulate cellular behaviours in complex scenarios. Then the performance of zosteric acid was tested under continuous flow conditions using the Center for Disease Control biofilm reactor (CDC bioreactor). We demonstrated that zosteric acid was active at 10 mg/L and it reduced microbial adhesion by 75% on both hydrophilic and hydrophobic surfaces. Results from CDC biofilm reactor studies showed a reduction of biofilm formation by 80%. These findings were confirmed by confocal microscopy. The control sample showed a dense multilayer network of yeast and filamentous forms whereas the treated sample exhibited an atypical biofilm architecture consisting of yeast cells and very few filamentous forms. In addition, FUN 1 viability staining and cryosections of biofilm samples indicated that zosteric acid induced a significant reduction in biofilm thickness (70%) while maintaining metabolically active cells. These findings suggested that zosteric acid significantly reduced C. albicans adhesion and its dimorphic switching from yeast to the filamentous form. These preliminary results are encouraging for the use of zosteric acid as a preventive approach against deleterious Candida albicans biofilm.