A new study involving the Medical University of Vienna shows how the multi-resistant fungus Candida auris utilises carbon dioxide (CO₂) to survive on the skin and become resistant to antifungal therapies. The research team identified several new targets that could be used in the future to curb the spread and infections caused by Candida auris. Due to its rapid development of resistance to almost all available antifungal drugs, the World Health Organisation (WHO) classifies the pathogen as a priority fungal pathogen.
The human pathogenic fungus Candida auris poses a significant health risk worldwide. Due to its pronounced adhesion properties, it grows predominantly on the skin surface and spreads rapidly in hospitals, especially via skin contact. For immunocompromised patients, colonisation and subsequent infections are life-threatening, with mortality rates of up to 70 per cent reported.
A study published in Nature Microbiology now shows for the first time that Candida auris uses a CO₂-based metabolic strategy to survive in the nutrient-poor conditions of the skin and to better tolerate antifungal therapies – especially amphotericin B (AMB). The work was carried out in close collaboration between the groups led by Adelheid Elbe-Bürger (MedUni Vienna) and Karl Kuchler (Max Perutz Labs Vienna).
CO₂ as fuel for energy production and resistance
Using multi-omics analyses, first author Trinh Phan-Canh, a doctoral student at MedUni Vienna, identified a key enzyme, carbonic anhydrase, which enables the fungus to convert small amounts of CO₂ into usable metabolic products. This allows Candida auris to generate mitochondrial energy and compensate for both nutrient deficiency and therapeutic stress.
"Candida auris uses minimal CO₂ concentrations to maintain its energy production and survive stress caused by antifungal drugs. This ability gives it a decisive survival advantage – especially on the skin surface," explains Adelheid Elbe-Bürger from the Department of Dermatology at the Medical University of Vienna.
Cooperation with the skin microbiome as a further survival factor
The study also shows that Candida auris cooperates with certain urease-positive bacteria in the skin microbiome. These bacteria break down urea, which reaches the skin via the sweat glands, into CO₂ – an additional source of energy for the fungus. This microbiological association could be a decisive factor in the high colonisation and transmission rates in hospitals.
From an infection prevention perspective, this opens up new avenues of approach: inhibiting bacterial urease activity could reduce local CO₂ concentrations and thus make colonisation by Candida auris more difficult.
New therapeutic targets along the CO₂ signalling pathway
The researchers identified several potential targets along the CO₂-dependent metabolic pathway. Of particular impact is the discovery that specific inhibition of mitochondrial cytochrome bc1 significantly weakens the energy metabolism of the fungus and increases the efficacy of amphotericin B (AMB), one of the few remaining and clinically most important antifungal agents for the treatment of Candida auris infections. A newly identified chemical compound that specifically inhibits cytochrome bc1 could thus form the basis for future antifungal drugs.
"Our results show that we can attack the fungus in completely new ways. The combination of metabolic inhibition and increased AMB efficacy opens up promising prospects for new therapies," adds Karl Kuchler from Max Perutz Labs.
Global problem with urgent need for new solutions
The number of severe Candida auris infections has been rising worldwide for more than 15 years, while the underlying mechanisms are still poorly understood. The new findings decipher key survival strategies of the pathogen and provide an important basis for the development of urgently needed therapeutic approaches.
