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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
PubMed

Insights

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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