A key enzyme enables a drug-resistant fungus to thrive on human skin, according to new research. Scientists have discovered that Candida auris, a notorious hospital fungus, has adapted to survive on human skin by harnessing carbon dioxide released at the surface. This metabolic advantage allows it to persist in areas where infections begin, endure treatment pressures, and spread unnoticed through healthcare settings. Skin colonization is a significant threat, as it turns people into silent reservoirs, enabling the fungus to move from body to bedrail without causing immediate illness. Researchers at the Medical University of Vienna documented this behavior by tracking the organism's viability on skin despite limited nutrients. Dermatologist Adelheid Elbe-Bürger linked this persistence to a newly described CO2-powered pathway that keeps the fungus metabolically active. This pathway also explains why skin colonization becomes a transmission point and why deeper vulnerabilities remain hidden initially. The team identified a single enzyme, carbonic anhydrase, which enables Candida auris to convert tiny CO2 leaks on skin into growth fuel. This conversion ensures the mitochondria's continued operation even with low sugar availability and helps the fungus withstand drug stress. When the researchers blocked the enzyme, the fungus struggled early, suggesting a potential target for stopping colonization before infections begin. The resistance to amphotericin B, a drug that can kill yeast cells, is a concern. Candida auris uses minimal CO2 concentrations to maintain energy production and survive stress caused by antifungal drugs, as explained by Elbe-Bürger. The CO2 link provides hospitals with a new weakness to exploit, as resistance to amphotericin B is rare in many yeasts. Skin bacteria also play a role, as Candida auris does not live alone, and nearby microbes can alter its fuel supply. The skin microbiome, a mix of bacteria and fungi on the skin, is a local CO2 source, with some bacteria carrying urease, an enzyme that breaks urea into ammonia and CO2. Blocking bacterial urease could lower CO2 on skin, but any real approach would need to protect beneficial microbes. Inside the fungus, energy production depends on a chain of proteins that pass electrons and build usable power. One link, cytochrome bc1, a mitochondrial complex that moves electrons for energy, proved easy to weaken in tests. A compound that inhibited cytochrome bc1 left Candida auris more vulnerable and boosted amphotericin B performance in the lab. This kind of combo could extend the life of older drugs, though researchers must still demonstrate safety in humans. Colonization happens in stages, starting on the skin surface with scarce food and low CO2 levels. When the team disrupted the CO2 pathway, the fungus struggled to establish itself on mouse skin and donated human skin. Later, once it reached deeper pockets like hair follicles, higher CO2 could partly compensate for the missing enzyme. The split suggests that prevention must focus on the first day or two, when colonization is still fragile. Candida auris can remain symptom-free on skin while quietly seeding rooms and equipment, making outbreak control challenging. The World Health Organization (WHO) has added the threat to a global priority list for dangerous fungal infections. For patients with weakened immune systems, invasive infections have shown death rates up to 70% in some reports. Because the fungus often resists multiple drugs at once, hospitals can lose time while treatment and isolation decisions catch up. Infection teams use current tools like isolation rooms, gloves, and careful cleaning, as clearing the fungus from skin can take time. Guidance from the Centers for Disease Control and Prevention emphasizes screening skin swabs and using specialized disinfectants on rooms and shared equipment. Treatment choices remain limited, with doctors often beginning with echinocandins for bloodstream infection, though resistant cases keep appearing. When those fail, amphotericin B becomes an option, but the drug can damage kidneys and requires close monitoring. If CO2-driven energy helps the fungus tolerate amphotericin B, combining it with energy blockers could restore sensitivity. Any combination therapy still needs trials, and clinicians must avoid pushing the fungus toward even broader resistance. This study links skin survival and drug tolerance to a shared energy pathway, making colonization itself a practical target. Next, researchers will need to test these inhibitors in patients and confirm that they block the fungus without damaging human cells. The study is published in the journal Nature.
