Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance

Abstract

Antimicrobial peptides (AMPs) are natural antibiotics produced by various organisms such as mammals, arthropods, plants, and bacteria. In addition to antimicrobial activity, AMPs can induce chemokine production, accelerate angiogenesis, and wound healing and modulate apoptosis in multicellular organisms. Originally, their antimicrobial mechanism of action was thought to consist solely of an increase in pathogen cell membrane permeability, but it has already been shown that several AMPs do not modulate membrane permeability in the minimal lethal concentration. Instead, they exert their effects by inhibiting processes such as protein and cell wall synthesis, as well as enzyme activity, among others. Although resistance to these molecules is uncommon several pathogens developed different strategies to overcome AMPs killing such as surface modification, expression of efflux pumps, and secretion of proteases among others. This review describes the various mechanisms of action of AMPs and how pathogens evolve resistance to them.

Low pH Enhances the Action of Maximin H5 against Staphylococcus aureus and Helps Mediate Lysylated Phosphatidylglycerol-Induced Resistance

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Antimicrobial peptides as natural bio-preservative to enhance the shelf-life of food

“…Generally, antimicrobial peptides interact with the membrane by the electrostatic interaction (Guilhelmelli et al 2013). Antimicrobial peptides have membrane permeabilizing action.…”

Immunomodulatory effects of anti-microbial peptides

“…It slowly became clear that the biophysical assumptions of neither of the two main membrane-perturbing models (barrel-stave and Shai-Matsuzaki-Huang carpet) are reliable for reaching structure-function conclusions [14]. The last push for alternative modes of action came after the observations that many AMPs fail to modulate membrane permeability at their microbiologically active concentration [15].…”