Candida albicans and Pseudomonas aeruginosa Interact To Enhance Virulence of Mucosal Infection in Transparent Zebrafish.

Polymicrobial infections often include both fungi and bacteria and can complicate patient treatment and resolution of infection. Cross-kingdom interactions among bacteria, fungi, and/or the immune system during infection can enhance or block virulence mechanisms and influence disease progression. The fungus and the bacterium are coisolated in the context of polymicrobial infection at a variety of sites throughout the body, including mucosal tissues such as the lung. , and have a bidirectional and largely antagonistic relationship. Their interactions remain poorly understood, specifically regarding host responses in mediating infection. In this study, we examine trikingdom interactions using a transparent juvenile zebrafish to model mucosal lung infection and show that and are synergistically virulent. We find that high burden, fungal epithelial invasion, swimbladder edema, and epithelial extrusion events serve as predictive factors for mortality in our infection model. Longitudinal analyses of fungal, bacterial, and immune dynamics during coinfection suggest that enhanced morbidity is associated with exacerbated pathogenesis and elevated inflammation. The quorum-sensing-deficient Δ mutant also enhances pathogenicity in coinfection and induces extrusion of the swimbladder. Together, these observations suggest that cross talk can benefit both organisms to the detriment of the host.