Strategies for the discovery and advancement of novel cationic antimicrobial peptides

Multi-drug resistant bacteria are appearing at an alarming rate and impose significant burdens on healthcare systems worldwide. Cationic peptides have shown great promise as broad spectrum antimicrobial agents with a demonstrated ability to kill resistant bacteria, however, issues such as protease susceptibility and toxicity issues have delayed their clinical development. This review summarizes recent progress in the advancement of cationic antimicrobial peptides for the treatment of bacterial infections. The major focus of the discussion relates to recent advances in the areas of screening and in silico modeling. A selection of novel strategies that diverge from classical linear α-peptide antimicrobials is also discussed. A diverse array of candidate structures will be key to the ultimate development of a stable platform for clinical development. The ability to accurately predict peptide activity in silico and in a high-throughput manner should benefit all classes of cationic antimicrobial peptides and provide a larger set of candidate structures for clinical evaluation.