title: Membrane perturbation action mode and structure-activity relationships of Protonectin, a novel antimicrobial peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes.
abstract: With the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is 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 α-helical confirmation in the membrane is essential for this action.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Dang
authors.forename: Jiexi
authors.initials: J
authors.lastname: Yan
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yan
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Junqiu
authors.initials: J
authors.lastname: Xie
authors.forename: Jindao
authors.initials: J
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D056004:Molecular Dynamics Simulation; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014688:Venoms / Q000737:chemistry*; D014863:Wasps / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D014688:Venoms