Recent progress in the study of the interactions of amphotericin B with cholesterol and ergosterol in lipid environments

Abstract

In the past decade substantial progress has been made in understanding the organization and biological activity of amphotericin B (AmB) in the presence of sterols in lipid environments. This review concentrates mainly on interactions of AmB with lipids and sterols, AmB channel formation in membranes, AmB aggregation, AmB modifications important for understanding its biological activity, and AmB models explaining its mechanism of action. Most of the reviewed studies concern monolayers at the water–gas interface, monolayers deposited on a solid substrate by use of the Langmuir–Blodgett technique, micelles, vesicles, and multi-bilayers. Liposomal AmB formulations and drug delivery are intentionally omitted, because several reviews dedicated to this subject are already available.

Selvamicin, an atypical antifungal polyene from two alternative genomic contexts

“…Such interactions can compromise membrane integrity and inhibit the function of membrane proteins (19,20). Recent studies suggest that ergosterol sequestration into extracellular aggregates may be the dominant mechanism of action (21,22), although several polyenes, including nystatin and amphotericin B, have also long been known to permeabilize membranes by the formation of ergosterol-dependent transmembrane channels (23).…”

New facets of antifungal therapy

“…65 Despite its long use, the exact mechanisms of action of amphotericin B remain unclear. 66 In the most traditional model, amphotericin B kills fungal cells by forming pores in ergosterol-containing membranes. More recent studies have proposed a variety of other possible mechanisms.…”

“…Amphotericin B can cause serious nephrotoxicity as well as electrolyte abnormalities and severe infusion-related reactions such as hypomagnesium, chills, fever, and rigors. 66,69 In view of this high toxicity but excellent efficacy, a drug structure or formulation modification was needed. Amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB) are combinations of amphotericin B and lipids in a specific ratio that improve the safety profile.…”

The influence of amphotericin B on the molecular organization and structural properties of DPPC lipid membranes modified by sterols

“…Until now, a lot of theoretical and experimental work has been carried out to understand the mode of AmB biological action [2,[5][6][7][8][9][10] and interaction with membranes [11][12][13][14]. The membrane activity of AmB is based on the fact that it has greater tendency to interact with ergosterol-enriched membranes of fungal cells than with mammalian membranes containing cholesterol, which was demonstrated in many studies especially regarding monolayers spread at the air-water interface [15][16][17][18][19].…”