Experimental concepts for linking the biological activities of antimicrobial peptides to their molecular modes of action

• Published in: Biochimica et biophysica acta. Biomembranes 2020-08, Vol.1862 (8), p.183275-183275, Article 183275
• Main Authors: Malanovic, Nermina, Marx, Lisa, Blondelle, Sylvie E., Pabst, Georg, Semeraro, Enrico F.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - therapeutic use; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - therapeutic use; Antimicrobial peptides; bacteria; Bacteria - drug effects; Bacteria - pathogenicity; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Cell Membrane - drug effects; Cell Membrane - microbiology; Cell Membrane Permeability - drug effects; DSC; Escherichia coli - drug effects; Escherichia coli - pathogenicity; Humans; MBC; Membrane fluidity; Membrane permeability; Membrane potential; MIC; Model systems; SAX/SANs; Zeta-potential
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2020.183275

The search for novel compounds to combat multi-resistant bacterial infections includes exploring the potency of antimicrobial peptides and derivatives thereof. Complementary to high-throughput screening techniques, biophysical and biochemical studies of the biological activity of these compounds enable deep insight, which can be exploited in designing antimicrobial peptides with improved efficacy. This approach requires the combination of several techniques to study the effect of such peptides on both bacterial cells and simple mimics of their cell envelope, such as lipid-only vesicles. These efforts carry the challenge of bridging results across techniques and sample systems, including the proper choice of membrane mimics. This review describes some important concepts toward the development of potent antimicrobial peptides and how they translate to frequently applied experimental techniques, along with an outline of the biophysics pertaining to the killing mechanism of antimicrobial peptides. [Display omitted] •Collection of available experimental techniques to characterize the modes of action of antimicrobial peptides.•Fundamental features of membrane-active antimicrobial peptide interactions with live bacteria and lipid-only membrane mimics.•Discussion of diverse aspects contributing to the identification of compromised membrane integrity, including critical assessment of advantages and limitations of different techniques and corresponding data interpretation.•Discussion of concepts that apply the comparison between live cells and model membranes.