Engineering the interaction of short antimicrobial peptides with bacterial barriers

While the rise of superbugs and new resistance mechanisms continues decreasing the effectiveness of classical antibiotics, antimicrobial peptides (AMPs) are emerging as a new class of antimicrobials. Still, several drawbacks limit their transition to the clinic, including high production cost, haemolytic activity and possible inactivation by proteases. Here, we give an overview of the most recent work on short AMPs, which are currently a minority in the AMP databases, and of the main AMP design rules, describing their application for short sequences. We also summarize the techniques that can serve to investigate the key steps of the antimicrobial action and that can aid in the engineering of a tuned AMP interaction with bacterial barriers. Particular emphasis is given to the relationship between peptide sequence features and interfacial behaviour, highlighting the role of AMPs self-assembly in the interaction with membranes and their antimicrobial activity.