Augmented Enterocyte Damage During Candida albicans and Proteus mirabilis Coinfection

The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast and the Gram-negative bacterium resulting in enhanced host cell damage. This synergistic effect was conserved across different isolates and occurred also with non- species and mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between and is induced by contact, but also by soluble factors. Specifically, we identified -mediated glucose consumption and farnesol production as potential triggers for virulence. In summary, our study demonstrates that coinfection of enterocytes with and can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.