Yadav Tara Chand, Gupta Payal, Saini Saakshi, Mohiyuddin Shanid, Pruthi Vikas, Prasad Ramasare
Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.
Department of Biotechnology, School of Sciences, P P Savani University, Surat 394125, Gujarat, India.
ACS Omega. 2022 Mar 1;7(10):8350-8363. doi: 10.1021/acsomega.1c05822. eCollection 2022 Mar 15.
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 and , 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 spp. Additionally, Chi-TY-AuNPs completely eradicated (100%) the mature biofilms of both the spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP-treated biofilm cells. The effect of Chi-TY-AuNPs on the ECM components showed significant reduction in protein content in the biofilm and substantial decrease in extracellular DNA content of both the spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the spp., whereas pronounced ROS production was observed in the Chi-TY-AuNP-treated biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP-treated cells, while inconsequential changes were observed in . Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in in response to Chi-TY-AuNPs except and . Conclusively, the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNPs in both the spp. Findings of the present study manifest Chi-TY-AuNPs as a potential therapeutic solution to biofilm-related chronic infections and overcome biofilm antifungal resistance.
在本研究中，制备了酪醇功能化壳聚糖金纳米粒子（Chi-TY-AuNPs）作为对抗真菌感染的替代治疗策略。使用了各种生物物理技术来表征合成的Chi-TY-AuNPs。评估了Chi-TY-AuNPs对[具体菌种1]和[具体菌种2]的抗真菌和抗生物膜活性，并努力阐明其可能的作用机制。Chi-TY-AuNPs对[具体菌种1]的固着细胞和浮游细胞均显示出高杀菌效果。此外，Chi-TY-AuNPs完全根除了（100%）两种[具体菌种]的成熟生物膜。场发射扫描电子显微镜（FESEM）分析突出了Chi-TY-AuNP处理的[具体菌种]生物膜细胞的形态变化。Chi-TY-AuNPs对细胞外基质（ECM）成分的影响显示，[具体菌种]生物膜中的蛋白质含量显著降低，两种[具体菌种]的细胞外DNA含量大幅下降。使用2',7'-二氯二氢荧光素二乙酸酯-碘化丙啶（DCFDA-PI）染色的活性氧（ROS）生成分析显示，两种[具体菌种]中的ROS水平都很高，而在Chi-TY-AuNP处理的[具体菌种]生物膜中观察到明显的ROS产生。生化分析显示，Chi-TY-AuNP处理的[具体菌种]细胞中麦角固醇含量降低，而[另一具体菌种]中观察到的变化不显著。此外，除了[某些特定基因]外，[具体菌种]中所选基因（麦角固醇生物合成、外排、固醇导入和葡聚糖生物合成）的转录表达因Chi-TY-AuNPs而降低。总之，结果显示了Chi-TY-AuNPs对两种[具体菌种]的生物膜抑制和生物膜根除效果。本研究结果表明Chi-TY-AuNPs是解决[具体菌种]生物膜相关慢性感染和克服生物膜抗真菌耐药性的潜在治疗方案。
