Increasing Heterogeneity in Antimicrobial Peptide Combinations Enhances Their Synergistic Activities

Antimicrobial peptides (AMPs) are short biopolymers produced by living organisms as an immune system defense against infections. They have been considered as potential alternatives to conventional antibiotics. Experiments suggest that combining several types of different AMPs might enhance their antimicrobial activity more effectively than using single-component AMPs. However, a clear understanding of the underlying microscopic mechanisms is still lacking. We present a theoretical investigation of antibacterial cooperativity mechanisms involving several types of AMPs. It is argued that synergy results from intermolecular interactions when the presence of one type of AMP stimulates the association of another type of AMP to bacteria. It is found that increasing the number of different AMPs in the mixtures increases the number of such interactions, making them more efficient in eliminating infections. Our theoretical framework provides valuable insights into the mechanisms of antimicrobial action.