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

Van Bambeke, Françoise;Mingeot-Leclercq, Marie-Paule;Brasseur, Robert;Tulkens, Paul M.;Schanck, André
(1996) Chemistry and Physics of Lipids — Vol. 79, n° 2, p. 123-135 (1996)

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Authors
  • Van Bambeke, Françoiseorcid-logoUCLouvain
    Author
  • Mingeot-Leclercq, Marie-PauleUCLouvain
    Author
  • Brasseur, Robert
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  • Tulkens, Paul M.UCLouvain
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  • Schanck, AndréUCLouvain
    Author
Abstract
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.
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Van Bambeke, F., Mingeot-Leclercq, M.-P., Brasseur, R., Tulkens, P. M., & Schanck, A. (1996). 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. Chemistry and Physics of Lipids, 79(2), 123-135. https://doi.org/10.1016/0009-3084(95)02520-0 (Original work published 1996)