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Superoxide dismutases are involved in Candida albicans biofilm persistence against Miconazole

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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 mu M. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since 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 compared to the expression levels in untreated sessile C. albicans cells. Moreover, addition of the superoxide dismutase inhibitor N,N'-diethyldithiocarbamate (DDC) to C. albicans biofilms resulted in an 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 an 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 Delta sod4 Delta sod5 mutant lacking Sods 4 and 5. Biofilms of the Delta sod4 Delta sod5 mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels 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.
Keywords
CELLS, LOCK THERAPY, CHEMOSENSITIZATION, INFECTION, GENE

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Chicago
Bink, Anna, Davy Vandenbosch, Tom Coenye, Hans Nelis, Bruno PA Cammue, and Karin Thevissen. 2011. “Superoxide Dismutases Are Involved in Candida Albicans Biofilm Persistence Against Miconazole.” Antimicrobial Agents and Chemotherapy 55 (9): 4033–4037.
APA
Bink, A., Vandenbosch, D., Coenye, T., Nelis, H., Cammue, B. P., & Thevissen, K. (2011). Superoxide dismutases are involved in Candida albicans biofilm persistence against Miconazole. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55(9), 4033–4037.
Vancouver
1.
Bink A, Vandenbosch D, Coenye T, Nelis H, Cammue BP, Thevissen K. Superoxide dismutases are involved in Candida albicans biofilm persistence against Miconazole. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2011;55(9):4033–7.
MLA
Bink, Anna, Davy Vandenbosch, Tom Coenye, et al. “Superoxide Dismutases Are Involved in Candida Albicans Biofilm Persistence Against Miconazole.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 55.9 (2011): 4033–4037. Print.
@article{1899747,
  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 mu M. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2\%. Since 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 compared to the expression levels in untreated sessile C. albicans cells. Moreover, addition of the superoxide dismutase inhibitor N,N'-diethyldithiocarbamate (DDC) to C. albicans biofilms resulted in an 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 an 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 Delta sod4 Delta sod5 mutant lacking Sods 4 and 5. Biofilms of the Delta sod4 Delta sod5 mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels 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.},
  author       = {Bink, Anna and Vandenbosch, Davy and Coenye, Tom and Nelis, Hans and Cammue, Bruno PA and Thevissen, Karin},
  issn         = {0066-4804},
  journal      = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
  keyword      = {CELLS,LOCK THERAPY,CHEMOSENSITIZATION,INFECTION,GENE},
  language     = {eng},
  number       = {9},
  pages        = {4033--4037},
  title        = {Superoxide dismutases are involved in Candida albicans biofilm persistence against Miconazole},
  url          = {http://dx.doi.org/10.1128/AAC.00280-11},
  volume       = {55},
  year         = {2011},
}

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