Cytotoxicity and resistance evolution of a novel antifungal carbon nanoparticle

Abstract

Antifungal drug resistance is a major problem in healthcare and agriculture. Synthesizing new drugs is one of the major mitigating strategies for overcoming this problem. In this context, carbon-dots (CDs) are a newer category of nanoparticles that have wide applications, potentially including use as antibiotics. However, there is a lack of understanding of the effect of long-term use of CDs as antimicrobials, particularly the ability of microbes to evolve resistance to antibiotic CDs. In this study, we synthesized novel florescent the bottom-up method using two antifungal drugs fluconazole and nourseothricin sulphate (ClonNAT). We first extensively characterized the physical properties of the newly synthesized carbon dots, Flu-Clo CDs. We measured the cytotoxicity of Flu-Clo CDs on budding yeast Saccharomyces cerevisiae and determined that it had comparable antifungal inhibition with extensively used drug fluconazole. Furthermore, we demonstrate that Flu-CLO CDs are not cytotoxic to human fibroblasts cell lines. Then, we quantified the ability of yeast to evolve resistance to Flu-Clo CDs. We evolved replicate laboratory yeast populations for 250 generations in the presence of Flu-Clo CDs or aqueous fluconazole. We found that yeast evolved resistance to Flu-Clo CDs and aqueous fluconazole at similar rates. Further, we found that resistance to Flu-Clo CDs conferred cross-resistance to aqueous fluconazole. Overall, the results demonstrate the efficacy of CDs as potential antifungal drugs. We can conclude that yeast populations can adapt quickly to novel antibiotics including CD based antibiotics, including CD-based antibiotics indicating the importance of proper use of antimicrobials in combating infections.