Antimicrobial Peptides: Vestiges of Past or Modern Therapeutics?

The ubiquitous occurrence of Antimicrobial Peptides (AMPs) in all domains of life emphasizes their crucial role as ancient mediators of host defense. Despite their antiquity and prolonged history of exposure to pathogens, endogenous AMPs continue to serve as effective antibiotics. An "evolutionary arms race" between host and pathogen resulted in structural diversity of AMPs, leading these molecules to retain activity against a wide range of pathogens, including antibiotic-resistant microbes. As the menace of antibiotic resistance continues to render most antibiotics ineffective against pathogens, the search for novel drug candidates has taken the center stage. The ability of AMPs to combat antibiotic-resistant microbes gave rise to a remarkable surge of interest in AMPs as potential therapeutics. Apart from being effective antimicrobials, AMPs have also found application as probes suitable for in-situ diagnosis of infection. Here, we review the evolutionary history of AMPs, their structural diversity, and mechanism of interaction with microbial membranes. We also summarize the role of AMPs as modern pharmaceuticals and challenges to this development.