Candida and Pseudomonas Interact to Enhance Mucosal Infection in Transparent Zebrafish
Abstract/ Summary
Polymicrobial communities exist throughout the human body and include both fungi and bacteria. During disease, cross-kingdom interactions among bacteria, fungi, and/or the immune system can alter virulence and lead to complex polymicrobial infections. The fungus C. albicans is among the most commonly isolated fungi in the context of fungal-bacterial co-infections and is often accompanied by the bacterium P. aeruginosa at a variety of sites throughout the body including mucosal tissues such as the lung. In vitro, C. albicans and P. aeruginosa have a cyclic, bi-directional, and largely antagonistic relationship, but these interactions do not account for the role of the host environment in mediating infection dynamics. Current in vivo infection models of C. albicans-P. aeruginosa infection demonstrate variable outcomes of infection and remain limited for characterizing immunopathology. In this study, we exploit the power of the juvenile zebrafish model to simultaneously characterize microbe-microbe interactions, microbial virulence, and immunopathology during C. albicans-P. aeruginosa mucosal infection to mimic the co-infected lung. We demonstrate that C. albicans and P. aeruginosa are synergistically virulent by using longitudinal analyses of fungal, bacterial and immune dynamics during co-infection, and suggest that enhanced morbidity is associated with exacerbated C. albicans pathogenesis and elevated inflammation. Altogether, our data suggest that C. albicans-P. aeruginosa crosstalk in vivo can benefit both organisms to the detriment of the host. This zebrafish infection model provides a foundation for future analyses of specific microbial and immune factors in mediating co-infection, and can be extended to study other clinically relevant fungal-bacterial infections by addressing unique questions regarding tri-kingdom interactions during polymicrobial infection.