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Resistant to most antifungal drugs, the yeast Candidozyma auris is spreading globally and has caused recent outbreaks in US hospitals. The US Centers for Disease Control and Prevention (CDC) classifies it as an urgent threat. To meet the need for better treatments, researchers at Carnegie Mellon University are developing a novel way to combat drug resistance.

There are currently few methods to control C. auris infections, which spread through contact. Most infections start on the skin and can enter the bloodstream if unchecked. The mortality rate is high for immunocompromised individuals.

In Chemical Engineering Journal, Tagbo Niepa, Camila Cu茅 Royo, and collaborators the potential of electrochemical therapy to treat C. auris, both alone and in combination with currently available antifungal drugs.

"We're trying to maximize the effects of drugs that are already available but are not working," says Cu茅 Royo, a Ph.D. student in chemical engineering.

Electrochemical therapy delivers a low dose of electrical current.

"The current is below our perception level, so we wouldn't even feel it on the skin," says Niepa, associate professor of chemical engineering and biomedical engineering. The technology has shown promise in eradicating bacteria and other species of yeast. Niepa and Cu茅 Royo's study is the first to describe its effect on C. auris.

They evaluated cell viability and metabolic functions under three different levels of electrical current. Their findings show that C. auris responds in a dose-dependent manner. Treatment with electrochemical therapy becomes more effective as the level of current increases.

Higher current levels have more effects on cell shape, structure, and other indicators of health. In response to the electrochemical stress, C. auris cells become hyperactive. Toxic material starts to accumulate in them, and they activate their internal machinery to try to clear it. Unable to recover from the stress, the cells eventually die. Higher current levels kill more cells.

At lower levels, electrochemical therapy damages cell membranes but does not kill C. auris. When Niepa and Cu茅 Royo tested a low level of electrical current in combination with a common class of antifungal drugs, they found that the two treatments, which do not work individually, can be effective in combination.

The antifungal drug caspofungin can interrupt the ability of C. auris to replicate, but it only works on cells that are metabolically active.

"Owing to their innate ability, C. auris cells commonly remain dormant when they are exposed to drugs in a biological environment. During that dormancy, the drug does not have an effect," says Niepa.

Before administering electrochemical therapy, Niepa and Cu茅 Royo observed antifungal drug molecules accumulating on C. auris cell walls. Healthy cells can control their permeability, and they do not allow the drug to diffuse in. After using a low level of electrical current to damage the cell walls, Niepa and Cu茅 Royo observed the drug molecules inside the cells.

For antifungal drugs that are currently ineffective, delivering them with a low dose of electrochemical therapy could make them more potent. The treatment method also has implications for the development of new drugs.

"If we're able to potentiate a drug, we can use a lower dose and minimize the possibility of resistance developing," says Cu茅 Royo.

Niepa has extensively studied the mechanisms of how electrochemical therapy works.

"We have a better understanding of our next step toward applications because we know exactly what is happening here," he says. With Cu茅 Royo and other collaborators, he is developing an electrochemical bandage that can be applied to the skin to treat C. auris and other infections.