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Antimicrob Agents Chemother. 2019 Jan 29;63(2). pii: e01555-18. doi: 10.1128/AAC.01555-18. Print 2019 Feb.

Monitoring of Fluconazole and Caspofungin Activity against In Vivo Candida glabrata Biofilms by Bioluminescence Imaging.

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VIB-KU Leuven Center for Microbiology, Leuven, Belgium.
Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
Center for Inflammation Research, VIB, Ghent, Belgium.
Department of Internal Medicine, Ghent University, Ghent, Belgium.
School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Research Group Microbial Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany.
Center for Sepsis Control and Care (CSCC), University Hospital Jena, Jena, Germany.
Institute for Microbiology, Friedrich Schiller University, Jena, Germany.
KU Leuven, Department of Microbiology and Immunology, Laboratory of Clinical Bacteriology and Mycology, Leuven, Belgium.
VIB-KU Leuven Center for Microbiology, Leuven, Belgium
Contributed equally


Candida glabrata can attach to various medical implants and forms thick biofilms despite its inability to switch from yeast to hyphae. The current in vivo C. glabrata biofilm models only provide limited information about colonization and infection and usually require animal sacrifice. To gain real-time information from individual BALB/c mice, we developed a noninvasive imaging technique to visualize C. glabrata biofilms in catheter fragments that were subcutaneously implanted on the back of mice. Bioluminescent C. glabrata reporter strains (luc OPT 7/2/4 and luc OPT 8/1/4), free of auxotrophic markers, expressing a codon-optimized firefly luciferase were generated. A murine subcutaneous model was used to follow real-time in vivo biofilm formation in the presence and absence of fluconazole and caspofungin. The fungal load in biofilms was quantified by CFU counts and by bioluminescence imaging (BLI). C. glabrata biofilms formed within the first 24 h, as documented by the increased number of device-associated cells and elevated bioluminescent signal compared with adhesion at the time of implant. The in vivo model allowed monitoring of the antibiofilm activity of caspofungin against C. glabrata biofilms through bioluminescent imaging from day four after the initiation of treatment. Contrarily, signals emitted from biofilms implanted in fluconazole-treated mice were similar to the light emitted from control-treated mice. This study gives insights into the real-time development of C. glabrata biofilms under in vivo conditions. BLI proved to be a dynamic, noninvasive, and sensitive tool to monitor continuous biofilm formation and activity of antifungal agents against C. glabrata biofilms formed on abiotic surfaces in vivo.


Candida glabrata ; animal models; antifungal agents; biofilms; bioluminescence imaging

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