title: Membrane active antimicrobial activity and molecular dynamics study of a novel cationic antimicrobial peptide polybia-MPI, from the venom of Polybia paulista.
abstract: As the frequent emergence of the resistant bacteria, the development of new agents with a new action mode attracts a great deal of interest. It is now widely accepted that antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics. In this study, antimicrobial peptide polybia-MPI and its analogs were synthesized and their antibacterial activity was studied. Our results revealed that polybia-MPI has potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Its ability to make PI permeate into bacteria and lead to the leakage of calcein from model membrane LUVs, suggests a killing mechanism involving membrane perturbation. SEM and TEM microscopy experiments verified that the morphology of bacteria was changed greatly under the treatment of polybia-MPI. Compared with the conventional chemotherapy, polybia-MPI targets the cell membrane rather than entering into the cell to exert its antibacterial activity. Furthermore, molecular dynamics (MD) simulations were employed to investigate the mechanism of membrane perturbation. The results indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity and the membrane disturbance by polybia-MPI is a cooperative process. In conclusion, with the increasing resistance to conventional antibiotics, there is no doubt that polybia-MPI could offer a new strategy to defend the resistant bacteria.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, PR China. wangkr@lzu.edu.cn
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Jiexi
authors.initials: J
authors.lastname: Yan
authors.forename: Wen
authors.initials: W
authors.lastname: Dang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.forename: Jindao
authors.initials: J
authors.lastname: Zhang
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Kai
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yan
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yang
authors.forename: Junqiu
authors.initials: J
authors.lastname: Xie
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004269:DNA, Bacterial / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry / Q000648:ultrastructure; D008563:Membrane Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D060327:Solid-Phase Synthesis Techniques; D014862:Wasp Venoms / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014863:Wasps
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; D008081:Liposomes; D008563:Membrane Lipids; D014862:Wasp Venoms; C582416:polybia-MPI, Polybia paulista