Amphotericin B resistance and membrane fluidity in Kluyveromyces lactis strains.
The membrane fluidity of reduced-amphotericin B (AmB)-sensitivity Kluyveromyces lactis mutant strain is higher than that of the wild-type K. lactis strain. After culture of the K. lactis and K. lactis mutant cells in the presence of subinhibitory doses of AmB (10 and 125 mg/liter, respectively), the plasma membranes of both yeast strains also showed a higher fluidity than did those of control cells. High membrane fluidity was associated with changes in the structural properties of the membranes. Culture of the K. lactis and K. lactis mutant cells in the presence of AmB induced changes in membrane lipid contents. In particular, phospholipid contents were increased in both strains treated with AmB, compared with their corresponding counterparts. As a result, the sterol/phospholipid ratio decreased. The relative proportion of monounsaturated fatty acids also increased after AmB treatment. The saturated fatty acid/monounsaturated fatty acid ratio decreased in K. lactis and K. lactis mutant cells treated with AmB but also in K. lactis mutant control cells compared to that in the K. lactis wild strain. These changes in lipid composition explain the higher fluidity, which could represent a process of metabolic resistance of the yeasts to AmB.
Younsi
M
M
Faculté de Pharmacie, Université Henri Poincaré, Nancy 1, UMR-CNRS 7564, LCPE Biochimie Microbienne, 54001 Nancy Cedex, France.
Ramanandraibe
E
E
Bonaly
R
R
Donner
M
M
Coulon
J
J
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002021:Buffers; D004352:Drug Resistance, Microbial / Q000502:physiology; D007700:Kinetics; D007716:Kluyveromyces / Q000187:drug effects* / Q000502:physiology; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000032:analysis; D009994:Osmolar Concentration; D013104:Spheroplasts / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000935:Antifungal Agents; D002021:Buffers; D008563:Membrane Lipids; D000666:Amphotericin B