The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR.
Amphotericin B (AmB) is a widely used polyene antibiotic to treat systemic fungal infections. This drug is known to be lethal to fungal cells but it has also side effect toxicity on mammalian cells. The mechanism of action of AmB is thought to be related to the difference of the main sterol present in the mammalian and the fungal cells, namely cholesterol and ergosterol, respectively. The effect of AmB has been investigated on pure dipalmitoylphosphatidylcholine (DPPC) and on cholesterol- and ergosterol-containing DPPC bilayers by 2H NMR spectroscopy. The 2H NMR results first confirm that AmB forms a complex with sterol-free DPPC bilayers, the interaction causing the structurization of the lipids and the increase of the gel-to-lamellar fluid DPPC phase transition temperature with increasing concentration of the antibiotic. The results also show that the effects of AmB on cholesterol- and ergosterol-containing DPPC bilayers are remarkably different. On one hand, the drug causes an increase of the orientational order of the lipid acyl chains in cholesterol-containing membranes, mostly in high cholesterol content membranes. On the other hand, the addition of AmB disorders the DPPC acyl chains when ergosterol is present. This is thought to be due to the direct complexation of the ergosterol by AmB, causing the sterol ordering effect to be weaker on the lipids.
Paquet
Marie-Josée
MJ
Département de Chimie, Centre de Recherche en Sciences et Ingénierie des Macromolécules, Université Laval, Québec, Canada.
Fournier
Isabelle
I
Barwicz
Joanna
J
Tancrède
Pierre
P
Auger
Michèle
M
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000666:Amphotericin B / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D003903:Deuterium; D004875:Ergosterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy
D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B; D002784:Cholesterol; D003903:Deuterium; D004875:Ergosterol