Antimicrobial peptides: to membranes and beyond

Background: Antimicrobial peptides (AMP) are widely recognized as promising alternatives to the current use of antibiotics and fungicides. Amino-acid sequences of a vast majority of AMP share cationic and amphipathic biophysical properties that allow their insertion into lipid bilayers and can lead to alteration of biological membrane functions. Initial characterization studies linked these properties to antimicrobial killing activity. However, further data indicate that this is not the sole mode of action and that more subtle mechanisms might mediate the interaction with and effect to target microbes, as well as the specificity and toxicity of peptides. As such, AMP are increasingly viewed as powerful multifunctional drugs. Objective: This review summarizes findings on these alternative non-lytic modes of antimicrobial action that go beyond membrane disruption, with an emphasis on the specific interaction with microbial cell wall/membrane components, signaling of AMP exposure and intracellular targets of peptide action. We also explore how novel technologies can help to reveal, characterize and exploit these antimicrobial properties. Conclusion: Detailed knowledge on non-lytic modes of action of AMP will help in the design and discovery of novel antibacterial and antifungal compounds.