Electrochemical Strategy for Eradicating Multi-Drug Resistant Candida Auris Using Low Level Direct Current and Echinocandins

The growing threat of antimicrobial organisms compromises even the most impervious healthcare systems. Candida auris, an emerging pathogen as recognized by the CDC, has proven to be not only highly lethal, but also extremely resistant to drug treatment. Various treatment methods have been proposed in addition to antifungals from essential oils to nanoparticles. One treatment form already proven effective at eradicating Candida spp. is electrochemical therapy (ECT) used in conjunction with drug treatment. At the highest current density tested (70μA/cm²), CFU studies reveal almost complete log killing of C. auris cells. Echinocandins are a novel drug class that due to their targeting of the (1,3)-β-D-glucan synthase have made resistance harder to develop. Therefore, their increased susceptibility makes them a useful tool for investigating antifungal diffusion properties and their potential for inhibiting cell growth. In this study, ECT is applied to C. auris cells and the effect of that treatment as well as the synergy between ECT and antifungal treatment on cell viability, function, and morphology are studied. Caspofungin, a commonly prescribed echinocandin for candidiasis, when applied to C. auris cells demonstrates rapid cell envelope adhesion, localizing to the cell wall within fifteen minutes. When caspofungin is incubated with the yeast cells for just as long, it enters the cells via endocytosis in vesicles. Upon further incubation, these vesicles rupture releasing the drug into the cell. Applying ECT lowers the energy barrier for endocytosis to occur, allowing for greater drug uptake. Visualizing fluorescently tagged caspofungin using confocal microscopy, these diffusion properties are analyzed. SEM images of the ECT-treated cells offer a look at how the electrical current affects cell morphology. Overall, this study demonstrates that ECT is a promising alternative strategy for effectively killing persistent yeast infections.