Plausible Mechanistic Insights in Biofilm Eradication Potential against Candida spp. Using In Situ-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 Candida albicans and C. glabrata, 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 Candida spp. Additionally, Chi-TY-AuNPs completely eradicated (100%) the mature biofilms of both the Candida spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP-treated Candida biofilm cells. The effect of Chi-TY-AuNPs on the ECM components showed significant reduction in protein content in the C. glabrata biofilm and substantial decrease in extracellular DNA content of both the Candida spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the Candida spp., whereas pronounced ROS production was observed in the Chi-TY-AuNP-treated C. glabrata biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP-treated C. glabrata cells, while inconsequential changes were observed in C. albican s. Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in C. glabrata in response to Chi-TY-AuNPs except ERG11 and CDR1. Conclusively, the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNPs in both the Candida spp. Findings of the present study manifest Chi-TY-AuNPs as a potential therapeutic solution to Candida biofilm-related chronic infections and overcome biofilm antifungal resistance.

Metal Nanoparticles to Combat Candida albicans Infections: An Update

“…PMAA-AgNPs had a spherical shape, mean diameter of 15 nm, and a Zeta potential of −41.83 mV. Zeta potential is a significant physiochemical attribute of nanosystems that can predict their interactions with different surfaces, playing a crucial role in drug delivery systems [ 21 ]. PMAA-AgNPs and FCZ reportedly exhibited synergistic interactions against C. albicans strains resistant to FCZ, leading to a reduction in MIC values and inhibition of germ tube formation.…”

“…Yadav et al [ 21 ] designed tyrosol-functionalized chitosan gold nanoparticles (Chi-TY-AuNPs). The intent was to use the Chi-TY-AuNPs as an alternative treatment strategy for Candida infections.…”

“…However, the exogenous mechanism underlying the antagonistic action of tyrosol against C. albicans has not been fully elucidated. Yadav et al [ 21 ] reported that Chi-TY-AuNPs had a Zeta potential of +45.5 mV and were spherical, with an average diameter in the range of 10−15 nm. These nanoparticles showed activity against C. albicans at 200 μg/mL, and the minimum fungicidal concentration was 800 μg/mL.…”

“…The ability of Chi-TY-AuNPs to inhibit C. albicans was associated with increased ROS production. Yadav et al [ 21 ] also evaluated the cytotoxicity of Chi-TY-AuNPs to NIH-3T3 fibroblast cells, and reported the absence of reduced cell viability, even when these nanoparticles were tested in higher concentrations. The finding highlighted the good biocompatibility of Chi-TY-AuNPs.…”

“…However, these antifungals may be limited in terms of toxicity, limited spectrum, relapse of infections, route of administration, high cost, availability, and the emergence of antifungal resistant strains of C. albicans [ 19 , 20 ]. To overcome these limitations, several studies have sought to identify new therapeutic strategies for candidiasis with a focus on nanotechnology [ 21 , 22 ].…”