The new anti-fungal mechanism of Amphotericin B in natural yeast membranes: quantifying the extraction of ergosterol
The activity of Amphotericin B against systemic fungal infections is widely accepted to result from its specific interaction with ergosterol. We have recently carried out a detailed characterization of the lipid composition and structure of native fungal membrane extracts from Pichia Pastoris, as well as the consequences of AmB action. The structure of yeast membranes differs considerably from typical model lipid bilayers composed of synthetic lipids and depends on the degree of lipid polyunsaturation. AmB inserts in yeast membranes both in the absence and presence of ergosterol, and our results confirmed directly that AmB forms a thick extra-membraneous aggregate, proposed recently to act as an ergosterol-extracting sponge responsible for the anti fungal activity instead of the classic model based on AmB pore formation. We propose to continue the previous investigation by quantifying ergosterol extraction by using membranes where the lipids and ergosterol are selectively labelled in turn. We will also investigate the ability of AmB to extract cholesterol found in mammalian membranes, to elucidate the mechanism of AmB's toxic side effects.
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FRAGNETO Giovanna; CANTU Laura; DELHOM Robin; HAERTLEIN Michael; JOUHET Juliette and WACKLIN KNECHT Hanna. (2015). The new anti-fungal mechanism of Amphotericin B in natural yeast membranes: quantifying the extraction of ergosterol. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-717
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