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

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.