5 years ago

Candida and Pseudomonas interact to enhance virulence of mucosal infection in transparent zebrafish.

Bergeron AC, Seman BG, Wheeler RT, Hogan DA, Archambault LS, Hammond JH
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 C. albicans and the bacterium P. aeruginosa are co-isolated in the context of polymicrobial infection at a variety of sites throughout the body, including mucosal tissues such as the lung. In vitro,C. albicans and P. aeruginosa have a bi-directional and largely antagonistic relationship. Their interactions in vivo remain poorly understood, specifically regarding host responses in mediating infection. In this study, we examine tri-kingdom interactions using a transparent juvenile zebrafish to model mucosal lung infection and show that C. albicans and P. aeruginosa are synergistically virulent. We find that high C. albicans 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 co-infection suggests that enhanced morbidity is associated with exacerbated C. albicans pathogenesis and elevated inflammation. The P. aeruginosa quorum sensing deficient ΔlasR mutant also enhances C. albicans pathogenicity in co-infection and induces extrusion of the swimbladder. Together, these observations suggest that C. albicans-P. aeruginosa crosstalk in vivo can benefit both organisms to the detriment of the host.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28847848

DOI: PubMed:28847848

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