Membrane raft lipid constituents affect drug susceptibilities of Candida albicans.

  • Pasrija R
  • Prasad T
  • Prasad R
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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.

Author-supplied keywords

  • Antifungal Agents
  • Antifungal Agents: pharmacology
  • Candida albicans
  • Candida albicans: drug effects
  • Candida albicans: genetics
  • Candida albicans: metabolism
  • Drug Resistance, Multiple, Fungal
  • Ergosterol
  • Ergosterol: metabolism
  • Fungal Proteins
  • Fungal Proteins: genetics
  • Fungal Proteins: metabolism
  • Membrane Microdomains
  • Membrane Microdomains: drug effects
  • Membrane Microdomains: metabolism
  • Microbial Sensitivity Tests
  • Sphingolipids
  • Sphingolipids: metabolism

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  • R Pasrija

  • T Prasad

  • R Prasad

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