Low-level direct currents eradicate multi-drug-resistant Candidozyma auris through physiological stress and antifungal permeation.

As multi-drug-resistant microorganisms continue to emerge and evolve, infections are becoming increasingly difficult to treat and, in some cases, life-threatening. Pathogens like Candidozyma auris pose serious challenges to healthcare, with new isolates exhibiting resistance to all available antifungal drugs. The demand for innovative therapies to effectively combat C. auris infections is greater than ever, given that this pathogen causes outbreaks globally. Electrochemical therapy (ECT) has recently gained interest due to its promising antimicrobial effects; however, its efficacy against C. auris remains unexplored. This study examines the mechanisms of ECT by analyzing its effects on cell viability, morphology, mitochondrial membrane potential, and reactive oxygen species (ROS) production in a clinical isolate of C. auris. Additionally, the synergy between ECT and the antifungal caspofungin (CSF) is explored to understand how ECT enhances drug diffusion and accumulation within C. auris cells. Results revealed a profound reduction in the pathogen's metabolic state, culminating in a 99.998 % killing efficiency with 70 μA/cm2 DC. Further analysis suggests that this reduction in cell viability is linked to alteration in key cellular functions, particularly membrane permeability. Notably, exposing C. auris to a sublethal current density of 17.5 μA/cm2 DC resulted in significant diffusion and intracellular accumulation of CSF, which presents a significant contrast to untreated C. auris cells. These findings provide new insights into the antimicrobial properties of ECT and its capacity to potentiate antifungal drugs, offering a promising strategy for managing C. auris-related infections.