CONICET | Buscador de Institutos y Recursos Humanos

Background: Candida albicans is one of the most common causative of opportunistic infections. Treatment of candidiasis is challenging considering the few antifungal drugsavailable and the increase in resistance. Antimicrobial photodynamic therapy (aPDT) isa recently developed therapeutic option that combines a non-toxic photosensitizer(PS) and light to kill the microbial pathogens. Targeting virulence, defined as the abilityof a pathogen to cause overt disease, represents another attractive target for thedevelopment of novel antifungal agents. Thymophylla pentachaeta (DC.) Small var.belenidium (DC.) is an endemic plant from Argentina in which the presence ofthiophenes, biologically active compounds whose antifungal activity is enhanced byirradiation with UVA, have been already described. Purpose: The purpose of this study was to evaluate the photodynamic antifungalactivity of hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and methanol(MeOH) extracts from T. pentachaeta var. belenidium and their inhibitory effects on C.albicans virulence factors as well as biofilm formation and eradication. Study Design/Methods: Antifungal photodynamic activity of hexane, dichloromethane,ethyl acetate and methanol extracts from different parts of the plant were assessed with the microbroth dilution, bioautography and the time-kill assays, under light anddarkness conditions. The capacities of the most active extracts of inhibiting Candidavirulence factors (adherence to epithelial cells, germ tube and pseudomyceliumformation and hydrolytic enzyme secretion) were assessed. In addition, the activityagainst biofilm formation and eradication has been investigated by reaction with 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) that quantifies living cells in thesestructures.Results: Hex and DCM extracts from T. pentachaeta roots exhibited high photodynamicantifungal activity against C. albicans (MFCs= 7.8 µg/ml) under UVA light irradiation.Chemical analysis of active extracts (Hex and DCM from roots) revealed the presenceof photoactive thiophenes. Both extracts generate reactive oxygen species throughtype I and II mechanisms. These extracts, at sub-inhibitory concentrations, under lightconditions decreased the adherence of C. albicans to Buccal Epithelial Cells (BEC),inhibited germ tube formation and reduced esterase production. Finally, theydemonstrated activity against preformed biofilms submitted to irradiation (MFCs= 3.91µg/ml and 15.63 µg/ml for Hex and DCM extracts, respectively). Conclusion: Taking together, results demonstrated the strong photodynamic effects ofT. pentachaeta root extracts under UVA irradiation, making them valuable alternativesto the already established antifungal drugs against C. albicans.

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