Aminoglycoside antibiotics prevent the formation of non-bilayer structures in negatively-charged membranes. Comparative studies using fusogenic (bis(beta-diethylaminoethylether)hexestrol) and aggregating (spermine) agents.
Aminoglycoside antibiotics cause aggregation but not fusion of negatively-charged liposomes at an extent proportional to their capacity to interact with acidic phospholipids (Van Bambeke et al., 1995, Eur. J. Pharmacol., 289, 321-333). To understand why aggregation is not followed by fusion, we have examined here the influence of two aminoglycosides with markedly different toxic potential (gentamicin > isepamicin) on lipid phase transition in negatively-charged liposomes using 31P-NMR spectroscopy, in comparison with spermine (an aggregating agent) and bis(beta-diethylaminoethylether)hexestrol or DEH (a fusogenic cationic amphiphile). Gentamicin, spermine, and, to a lesser extent, isepamicin inhibit the appearance of the isotropic signal seen upon warming of control liposomes and denoting the presence of mobile structures. This non-bilayer signal appeared most prominently when liposomes were incubated with DEH, a strong fusogenic agent. We conclude that aminoglycosides, like spermine, have the potential to prevent membrane fusion, by inhibiting the development of a critical change in membrane organization, which is associated with fusion. We suggest that this capacity could be a determinant in aminoglycoside toxicity.
van Bambeke
F
F
Université Catholique de Louvain, Brussels, Belgium.
Mingeot-Leclercq
M P
MP
Brasseur
R
R
Tulkens
P M
PM
Schanck
A
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004563:Electrochemistry; D005839:Gentamicins / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006589:Hexestrol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008561:Membrane Fusion / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry*; D008968:Molecular Conformation; D013096:Spermine / Q000737:chemistry / Q000494:pharmacology; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008081:Liposomes; D008563:Membrane Lipids; D006589:Hexestrol; D013096:Spermine; C016927:isepamicin; C100116:hexestrol bis(diethylaminoethyl ether)