Title: Superoxide dismutases are involved in Candida albicans biofilm persistence to miconazole
Authors: Bink, Anna
Vandenbosch, D.
Coenye, T.
Nelis, H.
Cammue, Bruno ×
Thevissen, Karin #
Issue Date: 2011
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial Agents and Chemotherapy vol:55 issue:9 pages:4033-4037
Abstract: We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in Candida albicans biofilms. Miconazole induced about 30% killing of sessile C. albicans cells at 75 µM. The fraction of miconazole-tolerant persisters, i.e. cells that can survive high doses of miconazole (0.6-2.4 mM), in these biofilms was 1-2%. As miconazole induces reactive oxygen species (ROS) in sessile C. albicans cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile C. albicans cells induced by miconazole as compared to the expression levels in untreated sessile C. albicans cells. Moreover, addition of the superoxide dismutase inhibitor N,N’-diethyldithio-carbamate (DDC) to C. albicans biofilms resulted in a 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of C. albicans clinical isolates with DDC resulted in 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in C. albicans biofilm persistence, we used a Δsod4Δsod5 mutant lacking Sods 4 and 5. Biofilms of Δsod4Δsod5 contained at least 3-fold less miconazole-tolerant persisters and had increased ROS levels as compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in C. albicans biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against C. albicans biofilms.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Centre of Microbial and Plant Genetics
× corresponding author
# (joint) last author

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