Early Transcriptional Adaptation of Candidozyma (Candida) auris During Interaction with Pseudomonas aeruginosa

Abstract

Bacterial–fungal polymicrobial infections are clinically important, but the early response of Candidozyma (Candida) auris to Pseudomonas aeruginosa remains incompletely understood. We investigated early fungal growth, extracellular glucose and metal availability, transcriptional adaptation, and pathogen burden using in vitro co-culture, RNA sequencing, nutrient measurements, and a murine co-infection model. Within 2 h, C. auris increased from 3.3 ± 0.6 × 106 to 7.1 ± 0.8 × 106 colony-forming units (CFU)/mL in monoculture, but reached only 4.9 ± 0.4 × 106 CFU/mL in co-culture. At 2 h, extracellular glucose concentrations were comparable between monoculture and co-culture despite reduced accumulation of viable C. auris cells in co-culture. Transcriptomics identified 210 upregulated and 124 downregulated genes, indicating remodelling of translation, carbon metabolism, stress responses, lipid metabolism, and cell-surface organization. Although iron-homeostasis genes were regulated, extracellular iron and zinc did not differ significantly at 2 h. Subsequently, extracellular iron concentration was significantly lower in co-culture at 4 h, whereas a reduction in zinc concentration at 6 h did not remain statistically significant. In vivo, co-infection reduced C. auris kidney burden by 1.4-log10, without significantly altering bacterial burden. These findings show that early bacterial interaction is associated with reduced fungal proliferation and induces transcriptional changes before detectable effects in extracellular iron and zinc, supporting a multifactorial interaction involving metabolic adaptation and subsequent environmental changes.