Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103
The pronounced skin tropism and pan-antifungal resistance of Candida auris pose a serious global health threat. A key question in C. auris biology is how clinical isolates acquire amphotericin B resistance. Here we demonstrate that a carbonic sensing pathway (CSP) contributes to amphotericin B resistance by modulating mitochondrial energy functions in clinical C. auris isolates. Integrated transcriptomics and proteomics identify the carbonic anhydrase Nce103 and its transcription factors Rca1 and Efg1 as important regulatory components of the CSP. The conversion of CO<sub>2</sub> into bicarbonate sustains energy metabolism required for colonization and fitness on human skin and in nutrient-limited microenvironments. We also show that bacterial skin colonizers engage urease to release CO<sub>2</sub> that sustains C. auris fitness and skin colonization. These findings highlight therapeutic options to re-sensitize C. auris to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.
Authors
- Irina Tsymala (ORCID: https://orcid.org/0000-0002-8515-5209)
- Anuradha Chowdhary (ORCID: https://orcid.org/0000-0002-2028-7462)
- Sabrina Jenull (ORCID: https://orcid.org/0000-0002-7478-1386)
- Cristina Coman (ORCID: https://orcid.org/0000-0002-3771-2410)
- Adelheid Elbe‐Bürger (ORCID: https://orcid.org/0000-0003-2461-0367)
- Trinh Phan-Canh (ORCID: https://orcid.org/0000-0002-6399-0959)
- G. Ianiri
- Tamires A. Bitencourt (ORCID: https://orcid.org/0000-0001-7373-3780)
- Robert Ahrends (ORCID: https://orcid.org/0000-0003-0232-3375)
- Diana Cerbu
- Philipp Penninger (ORCID: https://orcid.org/0000-0001-7487-2918)
- Saskia Seiser (ORCID: https://orcid.org/0000-0001-9339-2127)
- Markus Hartl (ORCID: https://orcid.org/0000-0002-4970-7336)
- Nina Troppmair (ORCID: https://orcid.org/0000-0002-3289-8316)
- Hossein Arzani (ORCID: https://orcid.org/0000-0002-8077-7586)
- Narakorn Khunweeraphong (ORCID: https://orcid.org/0000-0001-8457-2230)
- Lisa-Maria Zenz
- Andrej Knarr
- Karl Kuchler
- Doris Moser (ORCID: https://orcid.org/0000-0001-5680-1737)
- Harry L. T. Mobley
- Weiqiang Chen
- Christoph Müller
- Michaela Lackner
Institutions
- University of Delhi (IN)
- University of Molise (IT)
- University of Vienna (AT)
- Innsbruck Medical University (AT)
- Universität Innsbruck (AT)
- University of Michigan (US)
- Max Perutz Labs (AT)
- Medical University of Vienna (AT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2025-12-23
- DOI
- https://doi.org/10.1038/s41564-025-02189-z
- Citations
- 3
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 4.19