| Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells. | |
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MedLine Citation:
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PMID: 22354293 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous research has shown that 1% to 10% of sessile Candida albicans cells survive treatment with high doses of miconazole (a fungicidal imidazole). In the present study, we investigated the involvement of sphingolipid biosynthetic intermediates in this survival. We observed that the LCB4 gene, coding for the enzyme that catalyzes the phosphorylation of dihydrosphingosine and phytosphingosine, is important in governing the miconazole resistance of sessile Saccharomyces cerevisiae and C. albicans cells. The addition of 10 nM phytosphingosine-1-phosphate (PHS-1-P) drastically reduced the intracellular miconazole concentration and significantly increased the miconazole resistance of a hypersusceptible C. albicans heterozygous LCB4/lcb4 mutant, indicating a protective effect of PHS-1-P against miconazole-induced cell death in sessile cells. At this concentration of PHS-1-P, we did not observe any effect on the fluidity of the cytoplasmic membrane. The protective effect of PHS-1-P was not observed when the efflux pumps were inhibited or when tested in a mutant without functional efflux systems. Also, the addition of PHS-1-P during miconazole treatment increased the expression levels of genes coding for efflux pumps, leading to the hypothesis that PHS-1-P acts as a signaling molecule and enhances the efflux of miconazole in sessile C. albicans cells. |
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Authors:
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Davy Vandenbosch; Anna Bink; Gilmer Govaert; Bruno P A Cammue; Hans J Nelis; Karin Thevissen; Tom Coenye |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-02-21 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 56 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-13 Completed Date: 2012-08-17 Revised Date: 2013-04-01 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 2290-4 Citation Subset: IM |
Affiliation:
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Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antifungal Agents
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pharmacology* Candida albicans / drug effects, genetics*, metabolism Cell Membrane / drug effects, genetics, metabolism Drug Resistance, Fungal / drug effects, genetics* Gene Expression Regulation, Bacterial / drug effects* Membrane Transport Proteins / genetics, metabolism Miconazole / pharmacology* Mutation Phosphorylation Phosphotransferases (Alcohol Group Acceptor) / genetics, metabolism Saccharomyces cerevisiae / genetics, metabolism Saccharomyces cerevisiae Proteins / genetics, metabolism Signal Transduction / genetics Sphingosine / analogs & derivatives*, metabolism, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antifungal Agents; 0/Membrane Transport Proteins; 0/Saccharomyces cerevisiae Proteins; 0/phytosphingosine-1-phosphate; 123-78-4/Sphingosine; 22916-47-8/Miconazole; 554-62-1/phytosphingosine; 764-22-7/safingol; EC 2.7.1.-/LCB4 protein, S cerevisiae; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor) |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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