Document Detail

Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells.
MedLine Citation:
PMID:  22354293     Owner:  NLM     Status:  MEDLINE    
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.
Davy Vandenbosch; Anna Bink; Gilmer Govaert; Bruno P A Cammue; Hans J Nelis; Karin Thevissen; Tom Coenye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-21
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  56     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-13     Completed Date:  2012-08-17     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2290-4     Citation Subset:  IM    
Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
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MeSH Terms
Antifungal Agents / 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*
Phosphotransferases (Alcohol Group Acceptor) / genetics,  metabolism
Saccharomyces cerevisiae / genetics,  metabolism
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Signal Transduction / genetics
Sphingosine / analogs & derivatives*,  metabolism,  pharmacology
Reg. No./Substance:
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)

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