Membrane raft lipid constituents affect drug susceptibilities of Candida albicans.
By exploiting the biosynthetic pathways of raft lipid constituents, in this study we demonstrate that fluctuations in either sphingolipid or ergosterol levels result in increased drug sensitivity and morphological defects in Candida albicans cells. We show that any change in either ergosterol composition by conditionally disrupting ERG1 or in sphingolipid composition by homozygously disrupting its biosynthetic gene IPT1 leads to improper surface localization of a major ABC (ATP-binding cassette) drug efflux protein, Cdr1p. Results suggest that sterol/sphingolipid-rich membrane microdomains play an important role in positioning and functional maintenance of the integral efflux protein. The impaired ability of erg1/ipt1 mutant cells to efflux drugs mediated through Cdr1p appears to be the main cause of increased drug sensitivity of Candida cells.
Pasrija
R
R
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Prasad
T
T
Prasad
R
R
D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D026141:Drug Resistance, Multiple, Fungal; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D013107:Sphingolipids / Q000378:metabolism
D000935:Antifungal Agents; D005656:Fungal Proteins; D013107:Sphingolipids; D004875:Ergosterol