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Updated: Jul 6, 2026
Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
Published on: August 11, 2018
On the nature of antimicrobial activity: a model for protegrin-1 pores
Allison A Langham1, Abdallah Sayyed Ahmad, Yiannis N Kaznessis
1Department of Chemical Engineering and Materials Science, 421 Washington Avenue SE, Minneapolis, Minnesota 55455, USA.
Abstract:
We conducted over 150 ns of simulation of a protegrin-1 octamer pore in a lipid bilayer composed of palmitoyloleoyl-phosphatidylethanolamine (POPE) and palmitoyloleoyl-phosphatidylglycerol (POPG) lipids mimicking the inner membrane of a bacterial cell. The simulations improve on a model of a pore proposed from recent NMR experiments and provide a coherent understanding of the molecular mechanism of antimicrobial activity. Although lipids tilt somewhat toward the peptides, the simulated protegrin-1 pore more closely follows the barrel-stave model than the toroidal-pore model. The movement of ions is investigated through the pore. The pore selectively allows negatively charged chloride ions to pass through at an average rate of one ion every two nanoseconds. Only two events are observed of sodium ions crossing through the pore. The potential of mean force is calculated for the water and both ion types. It is determined that the chloride ions move through the pore with ease, similarly to the water molecules with the exception of a zone of restricted movement midway through the pore. In bacteria, ions moving through the pore will compromise the integrity of the transmembrane potential. Without the transmembrane potential as a countermeasure, water will readily flow inside the higher osmolality cytoplasm. We determine that the diffusivity of water through a single PG-1 pore is sufficient to cause fast cell death by osmotic lysis.
Insights
Antimicrobial peptides like protegrin-1 form pores in bacterial membranes, allowing chloride ions and water to pass. This ion and water transport disrupts the cell
Area of Science:
- Biophysics
- Molecular Biology
- Computational Chemistry
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity.
- Understanding the molecular mechanisms of AMPs is vital for developing new antibiotics.
- Protegrin-1 (PG-1) is a cationic antimicrobial peptide with a proposed pore-forming mechanism.
Purpose of the Study:
- To investigate the molecular mechanism of protegrin-1 pore formation in a bacterial inner membrane.
- To elucidate the ion and water transport dynamics through the protegrin-1 pore.
- To provide a computational model that complements experimental findings from NMR studies.
Main Methods:
- Molecular dynamics (MD) simulations of a protegrin-1 octamer pore.
- Simulations conducted in a lipid bilayer mimicking bacterial inner membrane (POPE/POPG).
- Calculation of potential of mean force (PMF) for water and ions (Cl-, Na+).
Main Results:
- The protegrin-1 pore structure aligns with the barrel-stave model.
- Chloride ions permeate the pore readily, while sodium ion passage is restricted.
- Water molecules exhibit high diffusivity through the pore, with a minor restriction zone.
- Calculated water and ion permeabilities suggest disruption of transmembrane potential.
Conclusions:
- The simulated protegrin-1 pore facilitates selective ion and water transport, leading to osmotic lysis.
- The findings support a model where PG-1 disrupts bacterial membrane integrity.
- This study provides a detailed molecular understanding of PG-1's antimicrobial action.
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