Antimicrobial Peptide Mechanisms Studied by Whole-Cell Deuterium NMR.

Sarika Kumari,Valerie Booth

doi:10.3390/ijms23052740

Abstract

Much of the work probing antimicrobial peptide (AMP) mechanisms has focussed on how these molecules permeabilize lipid bilayers. However, AMPs must also traverse a variety of non-lipid cell envelope components before they reach the lipid bilayer. Additionally, there is a growing list of AMPs with non-lipid targets inside the cell. It is thus useful to extend the biophysical methods that have been traditionally applied to study AMP mechanisms in liposomes to the full bacteria, where the lipids are present along with the full complexity of the rest of the bacterium. This review focusses on what can be learned about AMP mechanisms from solid-state NMR of AMP-treated intact bacteria. It also touches on flow cytometry as a complementary method for measuring permeabilization of bacterial lipid membranes in whole bacteria.

Highlights

Introduction to Antimicrobial PeptidesAntimicrobial peptides (AMPs) are a diverse class of molecules
Nuclear magnetic resonance (NMR) and circular dichroism (CD) studies reveal that indolicidin forms a well-defined extended structure in the presence of membrane-mimicking micelles [17,18]
AMPs bind in the polar head group region of the lipids, pushing the headgroups apart and inducing a positive curvature strain [26–28]

Summary

Introduction to Antimicrobial Peptides

Antimicrobial peptides (AMPs) are a diverse class of molecules. There have been thousands of AMP sequences reported to date [1]. The first group includes linear peptides with an α-helical structure, such as magainin and cecropin; as well as peptides rich in particular amino acids, such as glycine, proline, arginine, tryptophan, and histidine. Most of these peptides are unstructured in aqueous solution but become structured when in contact with lipids, trifluoroethanol, and detergent micelles [4]. In contrast with α-helical AMPs, the structure of these β-sheet peptides is less flexible because of the structural restraints introduced by the disulfide bonds between the β-strands This is the case, for example, with tachyplesin, protegrin, and human α-defensins [10,13]. Nuclear magnetic resonance (NMR) and circular dichroism (CD) studies reveal that indolicidin forms a well-defined extended structure in the presence of membrane-mimicking micelles [17,18]

Direct Killing of Target Cells by Permeabilizing the Membrane

Killing of Bacteria through Non-Membrane-Permeabilizing Mechanisms

AMP Interactions with Non-Lipid Cell Envelope Components of Bacteria