Antibacterial Activity And Action Mode Of A Novei Cationic Antimicrobial Peptide Protonectin

The misuse of antibiotics causes serious multidrug-resistance,which sounds the alarm that new antimicrobial agents with novel action mode are urgently needed.As a conserved conponent of host immune system,antimicrobial peptides(AMPs)are believed to be promising alternatives to conventional antibiotics.In this study,we aimed to study the antimicrobial activity and action mode of Protonectin,a cationic peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes.The results showed that Protonectin exhibited potent antimicrobial activity against a spectrum of bacteria,including multidrug-resistant strains.Its ability to make PI permeate into bacteria suggests a killing mechanism involving membrane perturbation.SEM microscopy experiments verified that the morphology of bacteria was changed greatly under the treatment of Protonectin.Compared with the conventional chemotherapy drugs,Protonectin targets the cell membrane rather than entering into the cell to exert its antibacterial activity.To further understand this mechanism,the structural features of Protonectin and its analogues were studied by circular dichroism(CD).The CD spectra demonstrated that Protonectin and its natural analogue Polybia-CP formed a typical ?-helical conformation in the membrane-mimicking environment,while its proline-substituted analogue had much lower or even no a-helix conformation.Molecular dynamics simulations indicated that the ?-helical conformation in the membrane was required for the exhibition of antibacterial activity.In conclusion,Protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane,and its a-helical conformation in the membrane is essential for this action.