Structure and mode of action of the antimicrobial peptide arenicin.
The solution structure and the mode of action of arenicin isoform 1, an antimicrobial peptide with a unique 18-residue loop structure, from the lugworm Arenicola marina were elucidated here. Arenicin folds into a two-stranded antiparallel beta-sheet. It exhibits high antibacterial activity at 37 and 4 degrees C against Gram-negative bacteria, including polymyxin B-resistant Proteus mirabilis. Bacterial killing occurs within minutes and is accompanied by membrane permeabilization, membrane detachment and release of cytoplasm. Interaction of arenicin with reconstituted membranes that mimic the lipopolysaccharide-containing outer membrane or the phospholipid-containing plasma membrane of Gram-negative bacteria exhibited no pronounced lipid specificity. Arenicin-induced current fluctuations in planar lipid bilayers correspond to the formation of short-lived heterogeneously structured lesions. Our results strongly suggest that membrane interaction plays a pivotal role in the antibacterial activity of arenicin.
Andrä
Jörg
J
Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 10, 23845 Borstel, Germany. jandrae@fz-borstel.de
Jakovkin
Igor
I
Grötzinger
Joachim
J
Hecht
Oliver
O
Krasnosdembskaya
Anna D
AD
Goldmann
Torsten
T
Gutsmann
Thomas
T
Leippe
Matthias
M
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D015801:Helminth Proteins; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015801:Helminth Proteins; D008051:Lipid Bilayers; D010455:Peptides; C496888:arenicin-1, Arenicola marina