Self‐Assembly of Linear, Natural Antimicrobial Peptides: An Evolutionary Perspective

Abstract Antimicrobial peptides are an ancient and innate system of host defence against a wide range of microbial assailants. Mechanistically, unstructured peptides undergo a secondary structure transition into amphipathic α‐helices, upon contact with membrane surfaces. This leads to peptide binding and removal of the membrane components in a detergent‐like manner or via self‐organisation into trans‐membrane pores (either barrel‐stave or toroidal pore) thereby destroying the microbe. Self‐assembly of antimicrobial peptides into oligomers and ultimately amyloid has been mostly examined in parallel, however recent findings link diseases, such as Alzheimer's disease as an aberrant activity of a protective neuropeptide with antimicrobial activity. These self‐assembled oligomers can also interact with membranes. Here, we review those antimicrobial peptides reported to self‐assemble into amyloid, where supported by structural evidence. We consider their membrane activities as antimicrobial peptides and present evidence of consistent self‐assembly patterns across major evolutionary groups. Trends are apparent across these groups, supporting the mounting data that self‐assembly of antimicrobial peptides into amyloid should be considered as synergistic to the antimicrobial peptide response.