Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.

2.50
Hdl Handle:
http://hdl.handle.net/10033/297477
Title:
Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.
Authors:
Heintz-Buschart, Anna; Eickhoff, Holger; Hohn, Erwin; Bilitewski, Ursula
Abstract:
Candida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans.
Affiliation:
Department of Biological Systems Analysis, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay. 2013, 164 (1):137-42 J. Biotechnol.
Journal:
Journal of biotechnology
Issue Date:
10-Mar-2013
URI:
http://hdl.handle.net/10033/297477
DOI:
10.1016/j.jbiotec.2012.12.004
PubMed ID:
23262131
Type:
Article
Language:
en
ISSN:
1873-4863
Appears in Collections:
publications of the research group compound profiling and screening (COPS)

Full metadata record

DC FieldValue Language
dc.contributor.authorHeintz-Buschart, Annaen_GB
dc.contributor.authorEickhoff, Holgeren_GB
dc.contributor.authorHohn, Erwinen_GB
dc.contributor.authorBilitewski, Ursulaen_GB
dc.date.accessioned2013-08-07T14:04:32Z-
dc.date.available2013-08-07T14:04:32Z-
dc.date.issued2013-03-10-
dc.identifier.citationIdentification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay. 2013, 164 (1):137-42 J. Biotechnol.en_GB
dc.identifier.issn1873-4863-
dc.identifier.pmid23262131-
dc.identifier.doi10.1016/j.jbiotec.2012.12.004-
dc.identifier.urihttp://hdl.handle.net/10033/297477-
dc.description.abstractCandida albicans is one of the most common opportunistic fungal pathogens, causing life-threatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast–hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model. We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promoter activity of the hyphae-specific HWP1 to β-galactosidase expression. In a pilot screening of 720 novel synthetic compounds, we identified substances which inhibited the outgrowth of germ tubes. They belonged to chemical classes not yet known for antimycotic properties, namely methyl aryl-oxazoline carboxylates, dihydrobenzo[d]isoxazolones and thiazolo[4,5-e]benzoisoxazoles. In conclusion we developed a novel screening assay, which addresses the morphological switch from the yeast form of C. albicans to its hyphal form and identified novel chemical structures with activity against C. albicans.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of biotechnologyen_GB
dc.titleIdentification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biological Systems Analysis, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_GB
dc.identifier.journalJournal of biotechnologyen_GB
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