Physicochemical Features and Peculiarities of Interaction of AMP with the Membrane

Abstract

Antimicrobial peptides (AMPs) are anti-infectives that have the potential to be used as a novel and untapped class of biotherapeutics. Modes of action of antimicrobial peptides include interaction with the cell envelope (cell wall, outer- and inner-membrane). A comprehensive understanding of the peculiarities of interaction of antimicrobial peptides with the cell envelope is necessary to perform a rational design of new biotherapeutics, against which working out resistance is hard for microbes. In order to enable de novo design with low cost and high throughput, in silico predictive models have to be invoked. To develop an efficient predictive model, a comprehensive understanding of the sequence-to-function relationship is required. This knowledge will allow us to encode amino acid sequences expressively and to adequately choose the accurate AMP classifier. A shared protective layer of microbial cells is the inner, plasmatic membrane. The interaction of AMP with a biological membrane (native and/or artificial) has been comprehensively studied. We provide a review of mechanisms and results of interactions of AMP with the cell membrane, relying on the survey of physicochemical, aggregative, and structural features of AMPs. The potency and mechanism of AMP action are presented in terms of amino acid compositions and distributions of the polar and apolar residues along the chain, that is, in terms of the physicochemical features of peptides such as hydrophobicity, hydrophilicity, and amphiphilicity. The survey of current data highlights topics that should be taken into account to come up with a comprehensive explanation of the mechanisms of action of AMP and to uncover the physicochemical faces of peptides, essential to perform their function. Many different approaches have been used to classify AMPs, including machine learning. The survey of knowledge on sequences, structures, and modes of actions of AMP allows concluding that only possessing comprehensive information on physicochemical features of AMPs enables us to develop accurate classifiers and create effective methods of prediction. Consequently, this knowledge is necessary for the development of design tools for peptide-based antibiotics.

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

“…AMPs are usually characterized by a stable secondary structure, in particular, the presence of β-sheets and α-helices [68]. A decrease in the ordering of AMPs, in particular, caused by the replacement of amino acid residues with sarcosine, can lead to a decrease in the antimicrobial properties of modified peptides [64].…”

Chitosan-Based Hydrogel for the Dual Delivery of Antimicrobial Agents Against Bacterial Methicillin-Resistant Staphylococcus aureus Biofilm-Infected Wounds

“… 31 Amphipathicity allows the peptides to attack the bacterial membrane by interacting with the hydrophobic–hydrophilic character of the lipids. 32 Amphipathic structure formation also determines hemolyticity, and therefore, a low amphipathic index gives a good indication of the biological activity as well as the hemolytic potential. 33 Lastly, the data filtration technology used allowed us to examine all peptides and their respective physicochemical properties to arrive at the best possible peptide that is suitable in our formulation experiments.…”

“…Even though hydrophobicity is required for bacterial membrane permeabilization, higher hydrophobicity than the optimum threshold can result in the loss of biological activity and an increase in toxicity . Amphipathicity allows the peptides to attack the bacterial membrane by interacting with the hydrophobic–hydrophilic character of the lipids . Amphipathic structure formation also determines hemolyticity, and therefore, a low amphipathic index gives a good indication of the biological activity as well as the hemolytic potential .…”

Antimicrobial Peptides: From Design to Clinical Application

“…Based on their structures, AMPs can be divided into four categories (Figure 1), including linear (bovine indolicidin [65]), α-helix (human cathelicidin LL-37 [66]), β-sheet (human α-defensin 6 [67]), and both α-helix and β-sheet peptides (human β-defensin-2 [68]). The structures of AMPs are changed according to environmental conditions, which is associated with the change of hydrophobicity and net charge of the cell membrane [69].…”