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How do the polyene macrolide antibiotics affect the cellular membrane properties?

Biochimica Et Biophysica Acta

|December 22, 1986

Summary

Polyene antibiotics like amphotericin B form pores in cell membranes, but their toxicity involves more than just pore formation. These drugs can also stimulate immune cells and synergize with other medications.

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Area of Science:

Biochemistry
Cell Biology
Pharmacology

Background:

Polyene antibiotics, including amphotericin B and nystatin, were understood to act by forming transmembrane pores.
The role of membrane sterols in polyene antibiotic action was established.
Recent data on unilamellar vesicles have revealed complexities in their mechanism of action.

Purpose of the Study:

To re-evaluate the mechanism of action of polyene antibiotics.
To investigate the factors influencing polyene antibiotic-induced membrane permeability.
To explore the multifaceted nature of polyene antibiotic toxicity and therapeutic potential.

Main Methods:

Studies on planar lipid monolayers, multilamellar phospholipid vesicles, and Acholeplasma laidlawii cells.
Analysis of unilamellar vesicles to assess membrane permeability.
Investigation of K+ leakage and lipid peroxidation in response to polyene antibiotics.

Main Results:

Polyene antibiotics can permeabilize gel-state membranes lacking sterols.
Multiple mechanisms of action may operate depending on conditions like antibiotic/lipid ratio and time.
Pore formation is not the sole cause of cell death; lipid peroxidation and colloid osmotic effects also contribute.
Sub-lethal concentrations can stimulate immune cells and cellular metabolism.
Polyene antibiotics can exhibit synergistic effects with other drugs.

Conclusions:

The mechanism of polyene antibiotic action is complex and not solely dependent on pore formation.
Toxicity involves multiple factors, including lipid peroxidation and osmotic effects.
Polyene antibiotics have potential non-detrimental effects, including immune stimulation and drug synergy.
The basis for selective antifungal toxicity is not always explained by sterol content differences.

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