Membrane permeability and antimicrobial peptides: Much more than just making a hole

Abstract

Antimicrobial peptides (AMPs) are one of the elements of innate immunity that have a crucial role in fighting infections. These molecules are produced by all kinds of cells and can display a wide spectrum of action against bacterial or fungal infections. Bacterial resistance toward broad‐spectrum antibiotics has become a major concern in recent years. In this context, AMPs have emerged as promising alternative therapy in response to this increasing problem because of their ability to inhibit growth and biofilm formation, even in drug‐resistant microorganisms. However, despite the myriad of patents filed related to AMPs, only a small proportion of AMPs have already received certification, either by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In order to pave the way of AMPs to certification, a comprehensive knowledge of the mechanism of action of these peptides is essential. Several models have been proposed to explain it and the permeabilization of the bacterial envelope seems to play a key role in most of them. In this review, we describe the different techniques that are generally used to assess the permeabilization induced by AMPs in either in vivo or in vitro systems. Additionally, a comprehensive analysis of the cooperation during the process of binding and permeabilization is included.

4-[(E)-2-(1-Pyrenyl)Vinyl]Pyridine Complexes: How to Modulate the Toxicity of Heavy Metal Ions to Target Microbial Infections

“…Indeed, the addition of lipophilic PyPe could temporarily form holes in the membrane and enable the entrance of metal ions into the bacteria. Such a formation of holes in cell membranes due to aromatic moieties is well documented for other molecules, e.g., pyrene, tryptophan, peptides, porphyrins, bipyridines, and substituted naphthols [38,[42][43][44][45]. The hypothesis of PyPe forming holes in bacterial membranes could be confirmed by the improvement ranges relating to the MIC.…”

Synergistic Effect, Improved Cell Selectivity, and Elucidating the Action Mechanism of Antimicrobial Peptide YS12

“…DPX works effectively as an indicator for cationic bindings on both purified LPS and whole bacterial cells [34]. However, DPX is nonfluorescent in free solution but exhibits high fluorescence when bound with LPS [35]. As seen in Figure 4a, peptide YS12 was bound to LPS by replacing the dansyl PMB and decreased fluorescence from 90% to 40% at 2.5 and 40 µg/mL, respectively.…”

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo

“…These agents are known to act on the cell membrane of bacterial pathogens stimulating the lysis and release of cytoplasmic contents. Furthermore, they can cross the membrane inhibiting different metabolic pathways in a bacterial cell and can modulate the antibacterial immune response [ 10 , 11 , 12 ]. AMPs have a series of advantages over conventional therapies such as a rapid bactericidal effect, low potential for inducing resistance, absence of the formation of active residues that can contaminate the environment, and action on MDR isolates [ 13 , 14 ].…”