usnic acid activity on oxidative and nitrosatide stress of azole-resistant candida albicans biofilm

Abstract

AbstractSeveral studies report about that (+)-usnic acid (UA), a secondary metabolite produced by lichens, inhibits growth of different bacteria, and fungi; however, mechanism of its antimicrobial activity remained unknown.In the present study, we have explored the ability of UA, obtained from Usnea amblyoclada, as an antibiofilm agent again stazole-resistant(RCa) and azole-sensitive (SCa) Candida albicansstrains by studying the cellular stress and antioxidant response in the biofilms. The biofilm inhibitory concentration (BIC) of UA (4 µg/mL) exhibited significant biofilm inhibition, 71.08% for RCa and 87.84% for SCa. Confocal scanning laser microscopy (CSLM) showed that in presence of UA the morphology of the mature biofilm was altered (reduced the biomass and thickness).The antifungal effect was mediated by an oxidative and nitrosative stress, with a significant accumulation of intracellular and extracellular ROS detected by CSLMand by nitro blue tetrazolium, respectively. Non-enzymatic and enzymatic antioxidant defenses increased in both strains compared to those of the 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.