Metabolic and Transcriptional alterations in Candida auris during Interaction with Pseudomonas aeruginosa

ABSTRACT: Polymicrobial bacterial–fungal infections are increasingly recognized as significant contributors to mortality in healthcare settings, particularly involving Pseudomonas aeruginosa and Candida species. While interactions between P. aeruginosaand Candida albicans have been widely studied, comparatively little is known about the emerging multidrug-resistant pathogen Candida auris. This study aimed to determine whether early growth inhibition of C. auris in co-culture with P. aeruginosa results from carbon depletion or micronutrient limitation, particularly iron restriction. Co-culture experiments demonstrated significantly reduced fungal proliferation despite preserved glucose availability, suggesting that carbon limitation is not the primary driver of growth inhibition. Transcriptomic analysis revealed strong upregulation of ribosome biogenesis and translation-associated genes, indicating increased translational capacity under competitive conditions. In contrast, genes involved in sterol and fatty acid biosynthesis, carbohydrate metabolism, and cell surface organization were consistently downregulated. Differential regulation of oxidative stress response genes suggested selective adaptation rather than generalized stress activation. Marked transcriptional changes were also observed in metal homeostasis pathways, with rapid extracellular iron depletion detected in co-culture conditions. Virulence-associated regulators, including genes linked to morphogenesis and adhesion, were downregulated, indicating reduced pathogenic potential. In a murine infection model, mixed infection resulted in significantly lower fungal burden compared to monoinfection, while bacterial burden remained unchanged. Together, these findings demonstrate that micronutrient competition, particularly iron limitation, plays a central role in shaping metabolic adaptation, transcriptional responses, and in vivo fitness of C. auris during interaction with P. aeruginosa.

ORGANISM(S): Candidozyma auris

PROVIDER: GSE327064 | GEO | 2026/04/08

REPOSITORIES: GEO