title: Plicatamide, an antimicrobial octapeptide from Styela plicata hemocytes.
abstract: Plicatamide (Phe-Phe-His-Leu-His-Phe-His-dc Delta DOPA), where dc Delta DOPA represents decarboxy-(E)-alpha,beta-dehydro-3,4-dihydroxyphenylalanine, is a potently antimicrobial octapeptide from the blood cells of the solitary tunicate, Styela plicata. Wild type and methicillin-resistant Staphylococcus aureus (MRSA) responded to plicatamide exposure with a massive potassium efflux that began within seconds. Soon thereafter, treated bacteria largely ceased consuming oxygen, and most became nonviable. Native plicatamide also formed cation-selective channels in model lipid bilayers composed of bacterial lipids. Methicillin-resistant S. aureus treated with plicatamide for 5 min contained prominent mesosomes as well as multiple, small dome-shaped surface protrusions that suggested the involvement of osmotic forces in its antimicrobial effects. To ascertain the contribution of the C-terminal dc Delta DOPA residue to antimicrobial activity, we synthesized several analogues of plicatamide that lacked it. One of these peptides, PL-101 (Phe-Phe-His-Leu-His-Phe-His-Tyr-amide), closely resembled native plicatamide in its antimicrobial activity and its ability to induce potassium efflux. Plicatamide was potently hemolytic for human red blood cells but did not lyse ovine erythrocytes. The small size, rapid action, and potent anti-staphylococcal activity of plicatamide and PL-101 make them intriguing subjects for future antimicrobial peptide design.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California 92093-0204, USA.
authors.forename: J Andy
authors.initials: JA
authors.lastname: Tincu
authors.forename: Lorenzo P
authors.initials: LP
authors.lastname: Menzel
authors.forename: Rustam
authors.initials: R
authors.lastname: Azimov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sands
authors.forename: Teresa
authors.initials: T
authors.lastname: Hong
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
authors.forename: Steven W
authors.initials: SW
authors.lastname: Taylor
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lehrer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects; D005260:Female; D006434:Hemocytes / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers; D009842:Oligopeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism; D014561:Urochordata / Q000502:physiology*
chemical_list: D008051:Lipid Bilayers; D009842:Oligopeptides; C407359:plicatamide; D011188:Potassium