Plausible Mechanistic Insights in Biofilm Eradication Potential against <i>Candida</i> spp. Using <i>In Situ</i> -Synthesized Tyrosol-Functionalized Chitosan Gold Nanoparticles as a Versatile Antifouling Coating on Implant Surfaces

Abstract

In the present study, tyrosol-functionalized chitosan gold nanoparticles (Chi-TY-AuNPs) were prepared as an alternative treatment strategy to combat fungal infections. Various biophysical techniques were used to characterize the synthesized Chi-TY-AuNPs. The antifungal and antibiofilm activities of Chi-TY-AuNPs were evaluated against <i>Candida albicans</i> and <i>C. glabrata</i>, and efforts have been made to elucidate the possible mechanism of action. Chi-TY-AuNPs showed a high fungicidal effect against both sessile and planktonic cells of <i>Candida</i> spp. Additionally, Chi-TY-AuNPs completely eradicated (100%) the mature biofilms of both the <i>Candida</i> spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP-treated <i>Candida</i> biofilm cells. The effect of Chi-TY-AuNPs on the ECM components showed significant reduction in protein content in the <i>C. glabrata</i> biofilm and substantial decrease in extracellular DNA content of both the <i>Candida</i> spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the <i>Candida</i> spp., whereas pronounced ROS production was observed in the Chi-TY-AuNP-treated <i>C. glabrata</i> biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP-treated <i>C. glabrata</i> cells, while inconsequential changes were observed in <i>C. albican</i> <i>s</i>. Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in <i>C. glabrata</i> in response to Chi-TY-AuNPs except <i>ERG11</i> and <i>CDR1</i>. Conclusively, the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNPs in both the <i>Candida</i> spp. Findings of the present study manifest Chi-TY-AuNPs as a potential therapeutic solution to <i>Candida</i> biofilm-related chronic infections and overcome biofilm antifungal resistance.