Bioluminescence imaging increases in vivo screening efficiency for antifungal activity against device-associated Candida albicans biofilms

Fungal infections are a major problem for a growing number of mostly immune-compromised patients. Candida albicans is an important human fungal pathogen causing mucosal and deep tissue infections of which the majority is associated with biofilm formation on medical implants. The animal models that are currently in use to test antifungal drugs are limited to ex vivo analyses, requiring host sacrifice that excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. As a solution, we introduce non-invasive, dynamic imaging and quantification of C. albicans biofilm formation in vivo and subsequent evaluation of treatment efficacy against these biofilms by using bioluminescent C. albicans in a catheter-associated mouse model. Bioluminescence imaging (BLI) allowed us to evaluate baseline biofilm load before start of therapy, which is necessary for the correct evaluation and interpretation of anti-biofilm efficacy in vivo. Moreover, we demonstrate that our BLI approach monitors the anti-biofilm activity of different antifungal agents efficiently in vitro and in vivo. In this study, BLI revealed superior anti-biofilm activity for echinocandins compared to amphotericin-B and fluconazole. In vitro, anidulafungin showed the highest anti-biofilm activity, followed by micafungin and caspofungin. In vivo, caspofungin significantly decreased the biofilm fungal load, as documented by the lower BLI signal and confirmed by CFU counts. In conclusion, our BLI approach increases the power and efficiency of screening and validation of antimycotics under both in vitro and in vivo conditions, thereby refining preclinical therapy studies.

Jaar van publicatie:2018

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:6

CSS-citation score:1

Authors from:Higher Education

Toegankelijkheid:Open