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Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells

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Abstract
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.
Keywords
SACCHAROMYCES-CEREVISIAE, BIOFILM FORMATION, DRUG-RESISTANCE, BUDDING YEAST, LIPID RAFTS, HEAT-STRESS, IN-VITRO, SPHINGOLIPIDS, FLUCONAZOLE, INHIBITION

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Chicago
Vandenbosch, Davy, Anna Bink, Gilmer Govaert, Bruno PA Cammue, Hans Nelis, Karin Thevissen, and Tom Coenye. 2012. “Phytosphingosine-1-phosphate Is a Signaling Molecule Involved in Miconazole Resistance in Sessile Candida Albicans Cells.” Antimicrobial Agents and Chemotherapy 56 (5): 2290–2294.
APA
Vandenbosch, D., Bink, A., Govaert, G., Cammue, B. P., Nelis, H., Thevissen, K., & Coenye, T. (2012). Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56(5), 2290–2294.
Vancouver
1.
Vandenbosch D, Bink A, Govaert G, Cammue BP, Nelis H, Thevissen K, et al. Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2012;56(5):2290–4.
MLA
Vandenbosch, Davy, Anna Bink, Gilmer Govaert, et al. “Phytosphingosine-1-phosphate Is a Signaling Molecule Involved in Miconazole Resistance in Sessile Candida Albicans Cells.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 56.5 (2012): 2290–2294. Print.
@article{2108213,
  abstract     = {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.},
  author       = {Vandenbosch, Davy and Bink, Anna and Govaert, Gilmer and Cammue, Bruno PA and Nelis, Hans and Thevissen, Karin and Coenye, Tom},
  issn         = {0066-4804},
  journal      = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
  keyword      = {SACCHAROMYCES-CEREVISIAE,BIOFILM FORMATION,DRUG-RESISTANCE,BUDDING YEAST,LIPID RAFTS,HEAT-STRESS,IN-VITRO,SPHINGOLIPIDS,FLUCONAZOLE,INHIBITION},
  language     = {eng},
  number       = {5},
  pages        = {2290--2294},
  title        = {Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells},
  url          = {http://dx.doi.org/10.1128/AAC.05106-11},
  volume       = {56},
  year         = {2012},
}

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