CONICET | Buscador de Institutos y Recursos Humanos

Several studies report that (+)-usnic acid (UA), a lichen secondary metabolite, inhibits growth of different bacteria and fungi; however, mechanism of its antimicrobial activity remains unknown. In this study, we have explored the ability of UA, obtained from Usnea amblyoclada, as an antibiofilm agent against azole-resistant (RCa) and azole-sensitive (SCa) Candida albicans strains by studying the cellular stress and antioxidant response in biofilms. The biofilm inhibitory concentration (BIC) of UA (4 µg/mL) exhibited a significant biofilm inhibition, 71.08% for RCa and 87.84% for SCa. Confocal scanning laser microscopy (CSLM) showed that the morphology of mature biofilm was altered (reduced the biomass and thickness) in the presence of UA. The antifungal effect was mediated by an oxidative and nitrosative stress, with a significant accumulation of intracellular and extracellular ROS detected by CSLM and by nitro blue tetrazolium, respectively. In fact, RCa and SCa biofilms treated at BIC of UA presented 30-fold and 10-fold increased ROS measurements compared to basal levels, respectively and important NO generation, showing 25-fold and 60-fold increased RNI levels with respect to the controls, respectively. Non-enzymatic and enzymatic antioxidant defenses were increased in both strains compared to biofilm basal levels as response to the increase of oxidant metabolites. The present study shows, for the first time, that UA can alter the prooxidant-antioxidant balance, which may be the cause of the irreversible cell damage and lead to cell death. Our results suggest that UA could be an alternative for the Candida infections treatment, which deserves further investigation.Keywords: Usnic acid; Usnea amblyoclada; Usneaceae; Candida albicans; Biofilms; prooxidant-antioxidant balance

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