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How Does the Antibiotic Amphotericin B Enter Membranes and What Does It Do There?
Sebastian Janik1, Rafal Luchowski1,2, Ewa Grela1,3
1Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, 20-031 Lublin, Poland.
The Journal of Physical Chemistry Letters
|April 26, 2024
Summary
Amphotericin B antifungal activity depends on ergosterol. This antibiotic forms membrane pores and clusters, disrupting fungal lipid membranes and function.
Area of Science:
- Biochemistry
- Molecular Biology
- Mycology
Background:
- Amphotericin B is a widely used antifungal antibiotic.
- Its precise mechanism of action on fungal membranes remains debated.
- Fungal cell membranes contain ergosterol, a key sterol.
Purpose of the Study:
- To investigate the mechanism of Amphotericin B incorporation into lipid membranes.
- To analyze the molecular reorganization of membranes induced by Amphotericin B.
- To elucidate the relationship between membrane alterations and antifungal activity.
Main Methods:
- Utilized solid-supported phosphatidylcholine monolayers with ergosterol as a model fungal membrane.
- Employed atomic force microscopy (AFM) for high-resolution imaging.
- Used lifetime imaging fluorescence microscopy (LIFM) to study molecular dynamics.
Main Results:
- Amphotericin B internalization into membranes requires the presence of ergosterol.
- Observed the formation of intramembrane clusters of Amphotericin B dimers.
- Identified large membrane pores (approximately 15 nm in diameter) induced by the antibiotic.
- Demonstrated simultaneous multiple modes of action affecting membrane structure and function.
Conclusions:
- Ergosterol is essential for Amphotericin B's membrane interaction and antifungal efficacy.
- Amphotericin B disrupts fungal membranes by forming clusters and pores.
- These structural changes lead to the loss of membrane integrity and physiological functionality.
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