Reactive oxygen species-independent apoptotic pathway by gold nanoparticles in Candida albicans

Abstract

Candida albicans is the most common pathogenic fungus in humans, causing cutaneous and life-threatening systemic infections. In this study, we confirmed using propidium iodide influx that gold nanoparticles (AuNPs), which are promising materials for use as antimicrobial agents, did not affect the membrane permeability of C. albicans. Thus, the fungal cell death mechanisms induced by AuNPs were assessed at intracellular levels including DNA damage, mitochondrial dysfunction, and reactive oxygen species (ROS) overproduction. AuNPs interacted with C. albicans DNA leading to increased nuclear condensation and DNA fragmentation. Changes in the mitochondria induced by AuNPs involving mass, Ca2+ concentrations, and membrane potential indicated dysfunction, though the level of intracellular and mitochondrial ROS were maintained. Although ROS signaling was not disrupted, DNA damage and mitochondrial dysfunction triggered the release of mitochondrial cytochrome c into the cytosol, metacaspase activation, and phosphatidylserine externalization. Additionally, the AuNPs-induced apoptotic pathway was not influenced by N-acetylcysteine, an ROS scavenger. This indicates that ROS signaling is not linked with the apoptosis. In conclusion, AuNPs induce ROS-independent apoptosis in C. albicans by causing DNA damage and mitochondria dysfunction.