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

Antimicrobial Agents and Chemotherapy
Davy VandenboschTom Coenye

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...Continue Reading

References

Jan 1, 1988·Current Topics in Medical Mycology·Y Yoshida
Jun 15, 1995·Biochemical and Biophysical Research Communications·Y MiyakeT Kawasaki
Mar 1, 1994·Infection and Immunity·S P Hawser, L J Douglas
Dec 31, 1997·The Journal of Biological Chemistry·R C DicksonR L Lester
Jul 25, 1998·The Journal of Biological Chemistry·M M NagiecR C Dickson
Sep 18, 2002·Antimicrobial Agents and Chemotherapy·Daisuke KobayashiNaoki Watanabe
Nov 28, 2002·Biological Chemistry·Michel Bagnat, Kai Simons
Jan 27, 2005·Biotechnology Letters·Kris De SmetRoland Contreras
Jul 14, 2005·Medical Mycology·Pranab K MukherjeeMahmoud A Ghannoum
Dec 13, 2005·Trends in Cell Biology·Volker Wachtler, Mohan K Balasubramanian
May 30, 2006·Progress in Lipid Research·Robert C DicksonRobert L Lester
May 16, 2007·Antimicrobial Agents and Chemotherapy·Palani PerumalW LaJean Chaffin
Jun 8, 2007·The Journal of Biological Chemistry·Karin ThevissenIsabelle E J A François
Dec 17, 2008·Oral Diseases·C J SeneviratneL P Samaranayake
Sep 29, 2009·The Journal of Biological Chemistry·Isabelle E J A FrançoisKarin Thevissen
Feb 5, 2010·The Journal of Antimicrobial Chemotherapy·Davy VandenboschTom Coenye
Oct 6, 2010·Advances in Experimental Medicine and Biology·Christopher R GaultYusuf A Hannun
Oct 6, 2010·Advances in Experimental Medicine and Biology·Laura RiboniPaola Viani
Oct 6, 2010·Advances in Experimental Medicine and Biology·Robert C Dickson

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Biofilms

Biofilms are adherent bacterial communities embedded in a polymer matrix and can cause persistent human infections that are highly resistant to antibiotics. Discover the latest research on Biofilms here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.