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<p>The pronounced skin tropism and pan-antifungal resistance of <i>Candida auris</i> pose a serious global health threat. A key question in <i>C. auris</i> 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 <i>C. auris</i> 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 <i>C. auris</i> fitness and skin colonization. These findings highlight therapeutic options to re-sensitize <i>C. auris</i> to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.</p>

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Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Trinh Phan-Canh,
  • Cristina Coman,
  • Michaela Lackner,
  • Nina Troppmair,
  • Christoph Müller,
  • Diana Cerbu,
  • Saskia Seiser,
  • Philipp Penninger,
  • Irina Tsymala,
  • Narakorn Khunweeraphong,
  • Tamires Bitencourt,
  • Andrej Knarr,
  • Sabrina Jenull,
  • Hossein Arzani,
  • Lisa-Maria Zenz,
  • Giuseppe Ianiri,
  • Weiqiang Chen,
  • Anuradha Chowdhary,
  • Harry L. T. Mobley,
  • Markus Hartl,
  • Doris Moser,
  • Robert Ahrends,
  • Adelheid Elbe-Bürger,
  • Karl Kuchler

摘要

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 CO2 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 CO2 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.