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Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

Kaat De Cremer, Katrijn De Brucker, Ines Staes, Annelies Peeters, Freija Van den Driessche, Tom Coenye UGent, Bruno PA Cammue and Karin Thevissen (2016) SCIENTIFIC REPORTS. 6.
abstract
We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen-dependent tolerance mechanism. In line, a correlation between miconazole's fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N'-diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole's fungicidal activity against C. albicans biofilm cells.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ZINC PYRITHIONE, SUSCEPTIBILITY, EFFLUX PUMPS, OXIDATIVE STRESS, VAGINAL CANDIDOSIS, GENE-EXPRESSION DATA, ANTIFUNGAL AGENTS, FLUCONAZOLE RESISTANCE, SACCHAROMYCES-CEREVISIAE, MECHANISM
journal title
SCIENTIFIC REPORTS
Sci. Rep.
volume
6
article number
27463
pages
14 pages
Web of Science type
Article
Web of Science id
000377551400001
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
4.259 (2016)
JCR rank
10/64 (2016)
JCR quartile
1 (2016)
ISSN
2045-2322
DOI
10.1038/srep27463
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
8059806
handle
http://hdl.handle.net/1854/LU-8059806
date created
2016-09-02 17:22:34
date last changed
2016-12-21 15:41:48
@article{8059806,
  abstract     = {We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen-dependent tolerance mechanism. In line, a correlation between miconazole's fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N'-diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole's fungicidal activity against C. albicans biofilm cells.},
  articleno    = {27463},
  author       = {De Cremer, Kaat and De Brucker, Katrijn and Staes, Ines and Peeters, Annelies and Van den Driessche, Freija and Coenye, Tom and Cammue, Bruno PA and Thevissen, Karin},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {ZINC PYRITHIONE,SUSCEPTIBILITY,EFFLUX PUMPS,OXIDATIVE STRESS,VAGINAL CANDIDOSIS,GENE-EXPRESSION DATA,ANTIFUNGAL AGENTS,FLUCONAZOLE RESISTANCE,SACCHAROMYCES-CEREVISIAE,MECHANISM},
  language     = {eng},
  pages        = {14},
  title        = {Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms},
  url          = {http://dx.doi.org/10.1038/srep27463},
  volume       = {6},
  year         = {2016},
}

Chicago
De Cremer, Kaat, Katrijn De Brucker, Ines Staes, Annelies Peeters, Freija Van den Driessche, Tom Coenye, Bruno PA Cammue, and Karin Thevissen. 2016. “Stimulation of Superoxide Production Increases Fungicidal Action of Miconazole Against Candida Albicans Biofilms.” Scientific Reports 6.
APA
De Cremer, Kaat, De Brucker, K., Staes, I., Peeters, A., Van den Driessche, F., Coenye, T., Cammue, B. P., et al. (2016). Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms. SCIENTIFIC REPORTS, 6.
Vancouver
1.
De Cremer K, De Brucker K, Staes I, Peeters A, Van den Driessche F, Coenye T, et al. Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms. SCIENTIFIC REPORTS. 2016;6.
MLA
De Cremer, Kaat, Katrijn De Brucker, Ines Staes, et al. “Stimulation of Superoxide Production Increases Fungicidal Action of Miconazole Against Candida Albicans Biofilms.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.