Antibiotic
resistance is one of the greatest challenges of our
time. This global health problem originated from a paucity of truly
effective antibiotic classes and an increased incidence of multi-drug-resistant
bacterial isolates in hospitals worldwide. Indeed, it has been recently
estimated that 10 million people will die annually from drug-resistant
infections by the year 2050. Therefore, the need to develop out-of-the-box
strategies to combat antibiotic resistance is urgent. The biological
world has provided natural templates, called antimicrobial peptides
(AMPs), which exhibit multiple intrinsic medical properties including
the targeting of bacteria. AMPs can be used as scaffolds and, via engineering, can be reconfigured for optimized potency
and targetability toward drug-resistant pathogens. Here, we review
the recent development of tools for the discovery, design, and production
of AMPs and propose that the future of peptide drug discovery will
involve the convergence of computational and synthetic biology principles.