A key enzyme enables a drug-resistant fungus to thrive on human skin, posing a significant threat to healthcare settings. Scientists have discovered that Candida auris, a notorious hospital fungus, has adapted to survive on human skin by utilizing carbon dioxide released at the surface. This metabolic advantage allows it to persist in areas where infections begin, withstand treatment pressures, and spread unnoticed through healthcare environments. Skin colonization is a major concern 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 serves as 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 scarce sugar availability and helps the fungus withstand drug stress. When the researchers blocked the enzyme, the fungus struggled early on, suggesting that this enzyme could be a target for stopping colonization before infections begin. The resistance to amphotericin B, a drug that can kill yeast cells, is a cause for concern. Candida auris uses minimal CO2 concentrations to maintain its energy production and survive stress caused by antifungal drugs. Since resistance to amphotericin B is rare in many yeasts, the CO2 link provides hospitals with a new weakness to exploit. On human skin, Candida auris is not alone, and nearby microbes can alter its fuel supply. The researchers pointed to the skin microbiome, a mix of bacteria and fungi on the skin, as a local CO2 source. Some bacteria contain urease, an enzyme that breaks urea into ammonia and CO2, and sweat delivers urea daily. Blocking bacterial urease could lower CO2 on the skin, but any real approach would need to protect beneficial microbes. Inside the fungus, energy production relies 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 made Candida auris more vulnerable and enhanced 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 occurs 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 simultaneously, hospitals can lose time while treatment and isolation decisions are made. Infection teams use current tools such as 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 for bloodstream infection often begin with echinocandins, drugs that weaken fungal cell walls, though resistant cases continue to emerge. 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.
