Insect-derived Antimicrobial Peptides: A New Paradigm for Combating Multidrug-resistant Pathogens Through Novel Mechanisms and Translational Strategies

Millions of deaths worldwide are attributed to antibiotic-resistant infections, and the spread of an antimicrobial resistance crisis is a critical threat to public health. The selective pressure exerted by conventional antibiotics not only restricts microbial evolutionary pathways, accelerating the onset of resistance but also promotes the activation of several downstream mechanisms of resistance in a very complex and interdependent manner. Once activated, such mechanisms are intrinsically more challenging to inactivate when targeted independently. AMPs usually have activity on the basis of a nonspecific disruption of microbial membranes, a mechanism that significantly lowers the chances of the onset of resistance. AMPs are structurally and functionally diverse molecules, typically ranging from 10-65 amino acids in length, with strong enrichment of cationic and hydrophobic residues. On the basis of their structural features, AMPs are usually classified into distinct families, such as amino acid-rich peptides, cysteine-rich peptides, and α-helical peptides. This review presents a comprehensive and updated description of insect-derived AMPs, including information from the Insect Antimicrobial Peptide Database with pertinent literature sources.