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  • Title: Energy dependence and reversibility of membrane alterations induced by polyene macrolide antibiotics in Chlorella vulgaris.
    Author: Malewicz B, Borowski E.
    Journal: Nature; 1979 Sep 06; 281(5726):80-2. PubMed ID: 551270.
    Abstract:
    The requirement of metabolic energy for the interaction of polyene macrolide antibiotics with eukaryotic organisms remains a controversial subject (for review see ref. 1) It has been claimed that the lethal binding of these antibiotics to the sterol target component of the hydrophobic core of the membrane, in accordance with the model of de Kruijff and Demel, is an energy-dependent process. When energy production is reduced by removal of all metabolisable substrates or by adding metabolic inhibitors, polyene binding and antifungal effects are also reduced. Metabolic energy may be required to maintain binding site accessibility or to move antibiotic molecules to the active site. The interaction is also restricted at low temperatures, possibly because of the reduced thermal mobilities of the groups concerned with antibiotic uptake. However, it should be emphasised that the interaction of polyene macrolides with artificial lipid membranes is a purely physicochemical process, although the type of permeability pathways induced are similar to those observed in natural membranes. Using Chlorella vulgaris as a model organism, we demonstrate here that the interaction of polyene macrolides with sensitive cells and the induction of lethal membrane permeability changes are energy-dependent processes or purely physicochemical phenomena, depending on the structure of the antibiotic used.
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