Date of Award

Summer 2017

Level of Access

Open-Access Thesis

Degree Name

Master of Science (MS)

Department

Biochemistry

Advisor

Robert Wheeler

Second Committee Member

Julie Gosse

Third Committee Member

John Singer

Abstract

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.

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