A groundbreaking study from the Medical University of Vienna has unveiled how the multi-resistant fungus Candida auris utilizes carbon dioxide (CO₂) to thrive on human skin and resist antifungal treatments. This research has identified new potential targets that could help curb the spread of Candida auris infections. The World Health Organization (WHO) has classified this pathogen as a priority due to its rapid resistance development against most antifungal drugs.
Candida auris is a significant global health threat, particularly in hospital settings where it spreads quickly through skin contact. For patients with compromised immune systems, colonization and subsequent infections can be deadly, with mortality rates reaching up to 70 percent.
CO₂ as a Survival Mechanism
Published in Nature Microbiology, the study demonstrates for the first time that Candida auris employs a CO₂-based metabolic strategy to endure the nutrient-scarce conditions of the skin and better withstand antifungal therapies, notably amphotericin B (AMB). This research was a collaborative effort between Adelheid Elbe-Bürger’s team at MedUni Vienna and Karl Kuchler’s group at Max Perutz Labs Vienna.
The Role of Carbonic Anhydrase
Through multi-omics analyses, Trinh Phan-Canh, a doctoral student at MedUni Vienna, identified a crucial enzyme, carbonic anhydrase, which enables the fungus to convert small amounts of CO₂ into usable metabolic products. This adaptation allows Candida auris to generate mitochondrial energy, compensating for nutrient deficiencies 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.
Interaction with the Skin Microbiome
The study also reveals that Candida auris collaborates with certain urease-positive bacteria within the skin microbiome. These bacteria decompose urea, which is secreted via sweat glands, into CO₂, providing an additional energy source for the fungus. This microbiological partnership could be a key factor in the high colonization and transmission rates observed in hospitals.
From an infection prevention standpoint, this discovery suggests new strategies: inhibiting bacterial urease activity could lower local CO₂ levels, thereby hindering Candida auris colonization.
New Therapeutic Targets
Researchers have pinpointed several potential targets along the CO₂-dependent metabolic pathway. Notably, they found that specific inhibition of mitochondrial cytochrome bc1 significantly weakens the fungus’s energy metabolism and boosts the efficacy of amphotericin B (AMB), one of the few remaining potent antifungal agents against Candida auris. A newly discovered chemical compound that specifically inhibits cytochrome bc1 could form the foundation for future antifungal medications.
“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 Health Implications
The incidence of severe Candida auris infections has been escalating worldwide for over 15 years, yet the mechanisms behind its survival and resistance remain poorly understood. The new findings provide crucial insights into the pathogen’s survival strategies, offering a vital foundation for developing much-needed therapeutic approaches.
This breakthrough highlights the urgent need for innovative solutions to combat Candida auris, a pathogen that continues to pose a formidable challenge to global health. As researchers delve deeper into the fungus’s biology, the hope is that these discoveries will pave the way for more effective treatments, ultimately reducing the threat it poses to vulnerable populations worldwide.
