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Interaction of Tryptophan- and Arginine-Rich Antimicrobial Peptide with E. coli Outer Membrane-A Molecular Simulation
George Necula1, Mihaela Bacalum2, Mihai Radu2
1Department of Computational Physics and Information Technologies, Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, 077125 Magurele, Romania.
Abstract:
A short antimicrobial peptide (AMP), rich in tryptophan and arginine (P6-HRWWRWWRR-NH2), was used in molecular dynamics (MD) simulations to investigate the interaction between AMPs and lipopolysaccharides (LPS) from two E. coli outer membrane (OM) membrane models. The OM of Gram-negative bacteria is an asymmetric bilayer, with the outer layer consisting exclusively of lipopolysaccharide molecules and the lower leaflet made up of phospholipids. The mechanisms by which short AMPs permeate the OM of Gram-negative bacteria are not well understood at the moment. For this study, two types of E. coli OM membrane models were built with (i) smooth LPS composed of lipid A, K12 core and O21 O-antigen, and (ii) rough type LPS composed of lipid A and R1 core. An OmpF monomer from E. coli was embedded in both membrane models. MD trajectories revealed that AMP insertion in the LPS layer was facilitated by the OmpF-created gap and allowed AMPs to form hydrogen bonds with the phosphate groups of inner core oligosaccharides. OM proteins such as OmpF may be essential for the permeation of short AMPs such as P6 by exposing the LPS binding site or even by direct translocation of AMPs across the OM.
Insights
Short antimicrobial peptides (AMPs) can permeate Gram-negative bacteria outer membranes by interacting with lipopolysaccharides (LPS). Outer membrane proteins like OmpF may facilitate this process, aiding AMPs in reaching their targets.
Area of Science:
- Microbiology
- Biophysics
- Computational Biology
Background:
- Gram-negative bacteria possess a unique outer membrane (OM) with an asymmetric bilayer structure.
- The outer leaflet of the OM is composed of lipopolysaccharides (LPS), crucial for bacterial integrity and interaction with antimicrobial peptides (AMPs).
- Mechanisms of AMP permeation through the OM remain incompletely understood.
Purpose of the Study:
- To investigate the interaction between a specific antimicrobial peptide (P6) and lipopolysaccharide (LPS) from two distinct Escherichia coli outer membrane models.
- To elucidate the role of outer membrane proteins, specifically OmpF, in facilitating AMP interaction with LPS.
Main Methods:
- Utilized molecular dynamics (MD) simulations to model interactions between the antimicrobial peptide P6 and two types of E. coli OM models.
- Constructed OM models incorporating smooth LPS (lipid A, K12 core, O21 O-antigen) and rough LPS (lipid A, R1 core).
- Embedded an OmpF monomer within both OM models to assess its influence on AMP-LPS interactions.
Main Results:
- MD simulations demonstrated that the antimicrobial peptide P6 inserts into the LPS layer, with OmpF facilitating this insertion through a created gap.
- AMPs formed hydrogen bonds with phosphate groups of inner core oligosaccharides within the LPS layer.
- The presence of OmpF significantly influenced the interaction and potential translocation of AMPs across the OM.
Conclusions:
- Outer membrane proteins like OmpF are potentially essential for the permeation of short antimicrobial peptides across the OM.
- OmpF may facilitate AMP entry by exposing LPS binding sites or directly aiding in translocation.
- Understanding these interactions is key to developing novel strategies against Gram-negative bacterial infections.
