Journal of Biological Chemistry
Volume 278, Issue 15, 11 April 2003, Pages 13546-13553
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MECHANISMS OF SIGNAL TRANSDUCTION
Plicatamide, an Antimicrobial Octapeptide from Styela plicata Hemocytes*

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Plicatamide (Phe-Phe-His-Leu-His-Phe-His-dcΔDOPA), where dcΔDOPA represents decarboxy-(E)-α,β-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 dcΔDOPA 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.

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Published, JBC Papers in Press, February 4, 2003, DOI 10.1074/jbc.M211332200

*

This work was supported in part by awards from the Stein-Oppenheimer Endowment Fund and the National Sea Grant Program of the United States Department of Commerce, National Oceanic Atmospheric Administration Grant R/MP-93 (through the California Sea Grant College Program and the California State Resources Agency).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Preliminary studies were supported by a generous donation from the Kieckhefer Foundation.