title: Imaging the action of antimicrobial peptides on living bacterial cells.
abstract: Antimicrobial peptides hold promise as broad-spectrum alternatives to conventional antibiotics. The mechanism of action of this class of peptide is a topical area of research focused predominantly on their interaction with artificial membranes. Here we compare the interaction mechanism of a model antimicrobial peptide with single artificial membranes and live bacterial cells. The interaction kinetics was imaged using time-lapse fluorescence lifetime imaging of a fluorescently-tagged melittin derivative. Interaction with the synthetic membranes resulted in membrane pore formation. In contrast, the interaction with bacteria led to transient membrane disruption and corresponding leakage of the cytoplasm, but surprisingly with a much reduced level of pore formation. The discovery that pore formation is a less significant part of lipid-peptide interaction in live bacteria highlights the mechanistic complexity of these interactions in living cells compared to simple artificial systems.
authors.affiliation: School of Chemistry, University of Melbourne, Parkville, Victoria 3010, Australia. mlgee@unimelb.edu.au
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gee
authors.forename: Matthew
authors.initials: M
authors.lastname: Burton
authors.forename: Alistair
authors.initials: A
authors.lastname: Grevis-James
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
authors.forename: Sally
authors.initials: S
authors.lastname: McArthur
authors.forename: Enzo A
authors.initials: EA
authors.lastname: Palombo
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.forename: Andrew H A
authors.initials: AH
authors.lastname: Clayton
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D008555:Melitten / Q000031:analogs & derivatives / Q000494:pharmacology*; D008563:Membrane Lipids / Q000737:chemistry; D008567:Membranes, Artificial; D008856:Microscopy, Fluorescence; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008563:Membrane Lipids; D008567:Membranes, Artificial; D053835:Unilamellar Liposomes; D008555:Melitten; D015060:1,2-Dipalmitoylphosphatidylcholine