AMINOGLYCOSIDE ANTIBIOTICS PREVENT THE FORMATION OF NONBILAYER 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 negativ ely-charged liposomes at an extent proportional to their capacity to i nteract with acidic phospholipids (Van Bambeke et al., 1995, Eur. J. P harmacol., 289, 321-333). To understand why aggregation is not followe d by fusion, we have examined here the influence of two aminoglycoside s with markedly different toxic potential (gentamicin > isepamicin) on lipid phase transition in negatively-charged liposomes using P-31-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, isepamici n 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 incu bated with DEH, a strong fusogenic agent. We conclude that aminoglycos ides, like spermine, have the potential to prevent membrane fusion, by inhibiting the development of a critical change in membrane organizat ion, which is associated with fusion. We suggest that this capacity co uld be a determinant in aminoglycoside toxicity.