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<p><i>Candida auris</i> is a critical priority fungal pathogen (World Health Organization). Clinical management is challenging, with high associated mortality, rapidly increasing antifungal resistance, and frequent nosocomial outbreaks. A critical bottleneck in understanding virulence is the lack of gene expression profiling models during infection. We developed a fish embryo yolk-sac microinjection model using <i>Aphanius dispar</i> (Arabian killifish; AK) at human body temperature. This enabled interrogation of infection dynamics <i>via</i> dual host-pathogen RNA-seq across five major clades of <i>C. auris</i> (I-V). Host responses included heat shock, complement activation, and nutritional immunity, notably haem oxygenase (<i>HMOX</i>) expression during clade IV infection. We identified a pathogen transcriptional signature across all five clades, strongly enriched for putative xenosiderophore transmembrane transporter candidate (<i>XTC</i>) genes. We describe this family and a sub-clade of five putative haem transport-related (<i>HTR</i>) genes. Only the basal clade V isolate formed filaments, associated with canonical and atypical regulators of morphogenesis. Clades I and IV demonstrated increased virulence, accompanied by up-regulation of three <i>HTR</i> genes in clade IV, and the non-mating mating-type locus (<i>MTL</i>) gene <i>PIKA</i> in both clades. Our study provides insights into <i>C. auris</i> pathogenesis, highlighting species-wide in vivo up-regulation of <i>XTC</i> genes during host tissue infection.</p>

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Xenosiderophore transporter gene expression and clade-specific filamentation in Candida auris killifish (Aphanius dispar) infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月19日

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  • Hugh Gifford,
  • Tina Bedekovic,
  • Nicolas Helmstetter,
  • Jack Gregory,
  • Qinxi Ma,
  • Alexandra C. Brand,
  • Duncan Wilson,
  • Johanna Rhodes,
  • Mark Ramsdale,
  • Tetsuhiro Kudoh,
  • Rhys A. Farrer

摘要

Candida auris is a critical priority fungal pathogen (World Health Organization). Clinical management is challenging, with high associated mortality, rapidly increasing antifungal resistance, and frequent nosocomial outbreaks. A critical bottleneck in understanding virulence is the lack of gene expression profiling models during infection. We developed a fish embryo yolk-sac microinjection model using Aphanius dispar (Arabian killifish; AK) at human body temperature. This enabled interrogation of infection dynamics via dual host-pathogen RNA-seq across five major clades of C. auris (I-V). Host responses included heat shock, complement activation, and nutritional immunity, notably haem oxygenase (HMOX) expression during clade IV infection. We identified a pathogen transcriptional signature across all five clades, strongly enriched for putative xenosiderophore transmembrane transporter candidate (XTC) genes. We describe this family and a sub-clade of five putative haem transport-related (HTR) genes. Only the basal clade V isolate formed filaments, associated with canonical and atypical regulators of morphogenesis. Clades I and IV demonstrated increased virulence, accompanied by up-regulation of three HTR genes in clade IV, and the non-mating mating-type locus (MTL) gene PIKA in both clades. Our study provides insights into C. auris pathogenesis, highlighting species-wide in vivo up-regulation of XTC genes during host tissue infection.