The fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans.

2.50
Hdl Handle:
http://hdl.handle.net/10033/269716
Title:
The fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans.
Authors:
Buschart, Anna; Burakowska, Anna; Bilitewski, Ursula
Abstract:
The fungicide fludioxonil is widely used in agriculture. Residua of this fungicide are occasionally detected in fruits and can therefore be ingested by humans. The human fungal pathogen Candida albicans expresses the target of fludioxonil, Nik1p, a type III histidine kinase involved in stress response. Inhibition of yeast and hyphae growth was hardly observable after treatment of C. albicans SC5314 with fludioxonil. As a side effect, however, we observed a concentration-dependent induction of the expression of the genes CDR1 and CDR2, encoding ATP-binding cassette (ABC) transporters. This was independent of the presence of the target of fludioxonil as induction was also observed in a Δnik1 deletion mutant. Deletion of the CDR1 gene aggravated the inhibition of germ tube formation by fludioxonil, indicating that, in the wild-type, the fungicide was discharged from the cell by Cdr1p. Cdr1p is also known as a resistance factor of C. albicans against the commonly used antimycotic fluconazole. Thus, the effect of concurrent exposure to fludioxonil and known cargoes of ABC transporters on their extrusion and the growth of C. albicans was examined. Pre-incubation with fludioxonil decreased the export rate of rhodamine 6G. The resistance to fluconazole was increased by fludioxonil, independently of Nik1p. Therefore, exposure of C. albicans to fludioxonil may lead to increased resistance to fluconazole treatment.
Affiliation:
Biological Systems Analysis, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
The fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans. 2012, 61 (Pt 12):1696-703 J. Med. Microbiol.
Journal:
Journal of medical microbiology
Issue Date:
Dec-2012
URI:
http://hdl.handle.net/10033/269716
DOI:
10.1099/jmm.0.050963-0
PubMed ID:
22918865
Type:
Article
Language:
en
ISSN:
1473-5644
Appears in Collections:
publications of the research group compound profiling and screening (COPS)

Full metadata record

DC FieldValue Language
dc.contributor.authorBuschart, Annaen_GB
dc.contributor.authorBurakowska, Annaen_GB
dc.contributor.authorBilitewski, Ursulaen_GB
dc.date.accessioned2013-02-18T15:19:02Z-
dc.date.available2013-02-18T15:19:02Z-
dc.date.issued2012-12-
dc.identifier.citationThe fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans. 2012, 61 (Pt 12):1696-703 J. Med. Microbiol.en_GB
dc.identifier.issn1473-5644-
dc.identifier.pmid22918865-
dc.identifier.doi10.1099/jmm.0.050963-0-
dc.identifier.urihttp://hdl.handle.net/10033/269716-
dc.description.abstractThe fungicide fludioxonil is widely used in agriculture. Residua of this fungicide are occasionally detected in fruits and can therefore be ingested by humans. The human fungal pathogen Candida albicans expresses the target of fludioxonil, Nik1p, a type III histidine kinase involved in stress response. Inhibition of yeast and hyphae growth was hardly observable after treatment of C. albicans SC5314 with fludioxonil. As a side effect, however, we observed a concentration-dependent induction of the expression of the genes CDR1 and CDR2, encoding ATP-binding cassette (ABC) transporters. This was independent of the presence of the target of fludioxonil as induction was also observed in a Δnik1 deletion mutant. Deletion of the CDR1 gene aggravated the inhibition of germ tube formation by fludioxonil, indicating that, in the wild-type, the fungicide was discharged from the cell by Cdr1p. Cdr1p is also known as a resistance factor of C. albicans against the commonly used antimycotic fluconazole. Thus, the effect of concurrent exposure to fludioxonil and known cargoes of ABC transporters on their extrusion and the growth of C. albicans was examined. Pre-incubation with fludioxonil decreased the export rate of rhodamine 6G. The resistance to fluconazole was increased by fludioxonil, independently of Nik1p. Therefore, exposure of C. albicans to fludioxonil may lead to increased resistance to fluconazole treatment.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of medical microbiologyen_GB
dc.subject.meshATP-Binding Cassette Transportersen_GB
dc.subject.meshAntifungal Agentsen_GB
dc.subject.meshCandida albicansen_GB
dc.subject.meshCandidiasisen_GB
dc.subject.meshCell Proliferationen_GB
dc.subject.meshDioxolesen_GB
dc.subject.meshDrug Resistance, Fungalen_GB
dc.subject.meshFluconazoleen_GB
dc.subject.meshFungal Proteinsen_GB
dc.subject.meshFungicides, Industrialen_GB
dc.subject.meshGene Expression Regulation, Fungalen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMembrane Transport Proteinsen_GB
dc.subject.meshMicrobial Sensitivity Testsen_GB
dc.subject.meshProtein Kinasesen_GB
dc.subject.meshPyrrolesen_GB
dc.subject.meshRhodaminesen_GB
dc.titleThe fungicide fludioxonil antagonizes fluconazole activity in the human fungal pathogen Candida albicans.en
dc.typeArticleen
dc.contributor.departmentBiological Systems Analysis, Helmholtz Centre for Infection Research, Braunschweig, Germany.en_GB
dc.identifier.journalJournal of medical microbiologyen_GB

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.