Name: amphotericin b and fungal membranes
Uploaded: 2026-03-12T13:35:53.000Z
Duration: 1 min 15 s
Channel: JoVE

Antifungal agents target pathogenic fungi to prevent infections from spreading. For example, amphotericin B is one such agent that targets the fungal cell membrane.Amphotericin B is an amphipathic molecule, containing both hydrophobic and hydrophilic regions.The mycosamine and carboxylic acid groups in the hydrophilic region bind to ergosterol, a sterol predominant in the fungal plasma membrane. This binding stabilizes the molecule&#8217;s insertion into the lipid bilayer.Once inserted, multiple amphotericin molecules align themselves with the surrounding lipid chains and assemble into pore-like channels.These channels allow the uncontrolled leakage of ions, especially potassium, which causes an osmotic imbalance and leads to fungal cell death.In another mechanism, amphotericin B molecules align parallel to the lipid bilayer.This orientation sequesters ergosterol toward the membrane surface, disrupting membrane structural integrity.

antifungal agents

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure&#8212;featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups&#8212;enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug&#8217;s antifungal activity, although weak binding to cholesterol contributes to toxicity in human cells.Mechanisms of Ergosterol TargetingAmphotericin B interacts with ergosterol through three complementary models:In the classic pore-formation model, amphotericin B-ergosterol complexes insert into the lipid bilayer, forming oligomeric transmembrane channels. These pores allow the uncontrolled leakage of intracellular ions, particularly potassium, disrupting ionic gradients and leading to cell death.In the surface-aligned model, amphotericin B binds ergosterol while remaining parallel to the membrane. This alignment causes clustering of ergosterol at the membrane surface, disrupting lipid organization and compromising membrane integrity&#8212;without forming pores.In the sponge model, amphotericin B aggregates sequester ergosterol into extracellular complexes. Rather than embedding in the membrane, these aggregates extract ergosterol, depleting it from the bilayer and impairing essential membrane functions.Reactive Oxygen Species and Oxidative StressBeyond its membrane-disrupting actions, amphotericin B also triggers the production of reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide, and hydroxyl radicals. These ROS cause oxidative damage to cellular components such as lipids, proteins, and nucleic acids. This oxidative stress operates independently of ergosterol binding, adding an additional mechanism to the drug&#8217;s fungicidal effects.

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic ...

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JoVE Core

Microbiology

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Antimicrobial Agents

KEY TERMS AND CONCEPTS

amphotericin b and fungal membranes

Amphotericin B targets fungal cell membranes by binding to ergosterol, a sterol found mainly in fungal plasma membranes. Its amphipathic structure helps this selective binding. It has a hydrophobic polyene-lactone ring and a hydrophilic region with mycosamine and carboxylic acid groups. Weak binding to cholesterol can also affect human cells and helps explain the drug’s toxicity.

One way amphotericin B kills fungi is through pore formation. In this model, amphotericin B-ergosterol complexes insert into the lipid bilayer and form oligomeric transmembrane channels. These pores let intracellular ions, especially potassium, leak out. The loss of ion balance disrupts the cell and leads to death.

Two other models describe how amphotericin B may work at the membrane surface. In the surface-aligned model, the drug binds ergosterol while staying parallel to the membrane. This causes ergosterol to cluster at the surface and disrupts lipid organization without making pores. In the sponge model, amphotericin B aggregates pull ergosterol out of the membrane into extracellular complexes. This depletes ergosterol from the bilayer and weakens membrane function.

Amphotericin B also causes oxidative stress. It can trigger reactive oxygen species, or ROS, such as superoxide anions, hydrogen peroxide, and hydroxyl radicals. These molecules damage lipids, proteins, and nucleic acids. This ROS-driven damage works independently of ergosterol binding and adds to the drug’s fungicidal effect.

Amphotericin B and Fungal Membranes

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Amphotericin B targets fungal cell membranes by binding to ergosterol, a sterol found mainly in fungal plasma membranes. Its amphipathic structure helps this selective binding. It has a hydrophobic polyene-lactone ring and a hydrophilic region with mycosamine and carboxylic acid groups. Weak binding to cholesterol can also affect human cells and helps explain the drug’s toxicity. One way amphotericin B kills fungi is through pore formation. In this model, amphotericin B-ergosterol complexes...

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key terms and concepts

Learn how amphotericin B targets ergosterol in fungal membranes, forms pores, disrupts membrane structure, and triggers oxidative stress in fungi.

Amphotericin B and Fungal Membranes | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

Amphotericin B and Fungal Membranes

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