A groundbreaking study from the Medical University of Vienna has unveiled how the multi-resistant fungus Candida auris leverages carbon dioxide (CO₂) to thrive on human skin and develop resistance to antifungal treatments. This research has pinpointed several potential targets for future therapies aimed at controlling the spread and infections caused by this formidable pathogen. The World Health Organization (WHO) has classified Candida auris as a priority fungal pathogen due to its alarming resistance to nearly all existing antifungal drugs.
The global health threat posed by the human pathogenic fungus Candida auris is significant. Its strong adhesion properties allow it to flourish on skin surfaces, facilitating rapid transmission in hospital settings, particularly through skin contact. For individuals with compromised immune systems, colonization and subsequent infections can be fatal, with mortality rates reaching up to 70 percent.
CO₂ as a Survival Mechanism
A recent study published in Nature Microbiology has, for the first time, demonstrated that Candida auris employs a CO₂-based metabolic strategy to endure the nutrient-scarce environment of the skin and to better withstand antifungal treatments, particularly amphotericin B (AMB). This research was a collaborative effort between teams led by Adelheid Elbe-Bürger from MedUni Vienna and Karl Kuchler from Max Perutz Labs Vienna.
Metabolic Adaptation and Resistance
Through multi-omics analyses, Trinh Phan-Canh, a doctoral candidate at MedUni Vienna, identified a pivotal enzyme, carbonic anhydrase, which enables the fungus to transform small quantities of CO₂ into usable metabolic products. This capability allows Candida auris to generate mitochondrial energy, thereby 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.
Interplay with the Skin Microbiome
The study further reveals that Candida auris collaborates with certain urease-positive bacteria within the skin microbiome. These bacteria decompose urea, which is secreted onto the skin through sweat glands, into CO₂, providing an additional energy source for the fungus. This microbiological interaction could be a critical factor in the high colonization and transmission rates observed in hospitals.
From an infection prevention standpoint, this discovery opens new avenues for intervention. By inhibiting bacterial urease activity, it may be possible to reduce local CO₂ concentrations, thereby hindering Candida auris colonization.
Potential Therapeutic Targets
The research team identified several promising targets along the CO₂-dependent metabolic pathway. Notably, the specific inhibition of mitochondrial cytochrome bc1 was found to significantly impair the fungus’s energy metabolism and enhance the effectiveness 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 serve as a foundation for developing future antifungal therapies.
“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.
A Global Health Challenge
Over the past 15 years, the incidence of severe Candida auris infections has surged worldwide, yet the underlying mechanisms remain poorly understood. These new findings elucidate key survival strategies of the pathogen, providing a crucial basis for the development of much-needed therapeutic approaches.
The announcement comes as the healthcare community continues to grapple with the challenges posed by drug-resistant pathogens. As researchers delve deeper into understanding Candida auris, the hope is that these insights will lead to innovative treatments that can effectively combat this global health threat.
