Gram-positive bacterial cell envelopes: The impact on the activity of antimicrobial peptides

Biochim Biophys Acta. 2016 May;1858(5):936-46. doi: 10.1016/j.bbamem.2015.11.004. Epub 2015 Nov 11.

Abstract

A number of cationic antimicrobial peptides, effectors of innate immunity, are supposed to act at the cytoplasmic membrane leading to permeabilization and eventually membrane disruption. Thereby, interaction of antimicrobial peptides with anionic membrane phospholipids is considered to be a key factor in killing of bacteria. Recently, evidence was provided that killing takes place only when bacterial cell membranes are completely saturated with peptides. This adds to an ongoing debate, which role cell wall components such as peptidoglycan, lipoteichoic acid and lipopolysaccharide may play in the killing event, i.e. if they rather entrap or facilitate antimicrobial peptides access to the cytoplasmic membrane. Therefore, in this review we focused on the impact of Gram-positive cell wall components for the mode of action and activity of antimicrobial peptides as well as in innate immunity. This led us to conclude that interaction of antimicrobial peptides with peptidoglycan may not contribute to a reduction of their antimicrobial activity, whereas interaction with anionic lipoteichoic acids may reduce the local concentration of antimicrobial peptides on the cytoplasmic membrane necessary for sufficient destabilization of the membranes and bacterial killing. Further affinity studies of antimicrobial peptides toward the different cell wall as well as membrane components will be needed to address this problem on a quantitative level. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.

Keywords: Antibacterial activity; Lipoteichoic acid; Membrane mimics; Peptidoglycan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Candida albicans / chemistry
  • Candida albicans / drug effects
  • Candida albicans / growth & development
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects*
  • Cell Wall / chemistry
  • Cell Wall / drug effects*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Fatty Acids / chemistry
  • Fatty Acids / pharmacology
  • Gram-Negative Bacteria / chemistry
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / chemistry
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / growth & development
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / pharmacology
  • Phospholipids / chemistry
  • Phospholipids / pharmacology
  • Species Specificity
  • Structure-Activity Relationship
  • Teichoic Acids / chemistry
  • Teichoic Acids / pharmacology

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Fatty Acids
  • Lipopolysaccharides
  • Phospholipids
  • Teichoic Acids
  • lipoteichoic acid