Impact of Metal-Functionalized Fullerenes on the Proliferation of Pathogenic Fungi
Abed Alqader Ibrahim1, Tariq Khan1, Dennis LaJeunesse1
1Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, United States.
Abstract:
Given the trajectory and prevalence of multidrug-resistant (MDR) organisms like Candida auris, the dearth of available antifungal drugs and the global need for effective therapeutics, the exploration of safe antifungals with broad-spectrum potential and novel antimicrobial mechanisms is imperative for future treatment strategies. Herein, the broad-spectrum potential of previously synthesized silver and copper coordinated chlorine functionalized fullerene nanoparticles (Ag-C60-Cl and Cu-C60-Cl) against two clinically significant fungal pathogens, Candida albicans and C. auris is investigated. The experimental results show enhanced antifungal activity of Ag-C60-Cl compared to Cu-C60-Cl, C60-Cl, and fluconazole. The minimum inhibitory concentrations (MIC) of Ag-C60-Cl and Cu-C60-Cl are 15.62 and 250 μg/mL, respectively, against C. albicans. Notably, the MIC of the Ag-C60-Cl against C. auris is 3.9 μg/mL, whereas the MIC of Cu-C60-Cl is 250 μg/mL. Analysis of fungal growth kinetics shows that Ag-C60-Cl significantly delayed the growth of C. albicans and suppressed the growth of C. auris. Mechanistic studies highlight that Ag-C60-Cl produced higher reactive oxygen species (ROS) and triggered catalase enzymes by acting as oxidants. Additionally, the NPs exhibited physical interactions with yeast cells, indicating a dual mode of action. These findings establish the potential of Ag-C60-Cl as a new and potentially transformative antifungal strategy against two clinically significant pathogens.
Insights
Silver and copper fullerene nanoparticles show promise as new antifungal agents. Silver fullerene nanoparticles (Ag-C60-Cl) demonstrated potent activity against Candida albicans and Candida auris, offering a potential new strategy against drug-resistant fungi.
Area of Science:
- Nanotechnology
- Materials Science
- Antimicrobial Research
Background:
- Rising prevalence of multidrug-resistant (MDR) fungal pathogens like Candida auris necessitates novel therapeutic strategies.
- Limited availability of effective antifungal drugs poses a significant global health challenge.
- Exploration of broad-spectrum antifungals with novel mechanisms is crucial for future treatment.
Purpose of the Study:
- To investigate the broad-spectrum antifungal potential of silver and copper coordinated chlorine functionalized fullerene nanoparticles (Ag-C60-Cl and Cu-C60-Cl).
- To evaluate the efficacy of these nanoparticles against clinically significant fungal pathogens, Candida albicans and Candida auris.
- To explore the underlying mechanisms of antifungal action.
Main Methods:
- Synthesis of silver and copper coordinated chlorine functionalized fullerene nanoparticles (Ag-C60-Cl, Cu-C60-Cl).
- Determination of minimum inhibitory concentrations (MIC) against Candida albicans and Candida auris.
- Analysis of fungal growth kinetics and mechanistic studies involving reactive oxygen species (ROS) production and catalase enzyme activity.
Main Results:
- Ag-C60-Cl exhibited significantly enhanced antifungal activity compared to Cu-C60-Cl, C60-Cl, and fluconazole.
- MIC values for Ag-C60-Cl were 15.62 μg/mL against C. albicans and 3.9 μg/mL against C. auris.
- Ag-C60-Cl significantly delayed C. albicans growth and suppressed C. auris growth, producing higher ROS and triggering catalase enzymes, indicating a dual mode of action.
Conclusions:
- Silver coordinated chlorine functionalized fullerene nanoparticles (Ag-C60-Cl) show potent broad-spectrum antifungal activity.
- Ag-C60-Cl presents a promising new therapeutic strategy against clinically significant fungal pathogens, including drug-resistant strains.
- The dual mode of action involving ROS production and physical interaction with yeast cells contributes to its antifungal efficacy.
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