title: Trichoplaxin - a new membrane-active antimicrobial peptide from placozoan cDNA.
abstract: A method based on the use of signal peptide sequences from antimicrobial peptide (AMP) precursors was used to mine a placozoa expressed sequence tag database and identified a potential antimicrobial peptide from Trichoplax adhaerens. This peptide, with predicted sequence FFGRLKSVWSAVKHGWKAAKSR is the first AMP from a placozoan species, and was named trichoplaxin. It was chemically synthesized and its structural properties, biological activities and membrane selectivity were investigated. It adopts an α-helical structure in contact with membrane-like environments and is active against both Gram-negative and Gram-positive bacterial species (including MRSA), as well as yeasts from the Candida genus. The cytotoxic activity, as assessed by the haemolytic activity against rat erythrocytes, U937 cell permeabilization to propidium iodide and MCF7 cell mitochondrial activity, is significantly lower than the antimicrobial activity. In tests with membrane models, trichoplaxin shows high affinity for anionic prokaryote-like membranes with good fit in kinetic studies. Conversely, there is a low affinity for neutral eukaryote-like membranes and absence of a dose dependent response. With high selectivity for bacterial cells and no homologous sequence in the UniProt, trichoplaxin is a new potential lead compound for development of broad-spectrum antibacterial drugs.
authors: Faculty of Science, University of Split, Nikole Tesle 12, 21000 Split, Croatia.
authors: Juraj
authors: J
authors: Simunić
authors: Max F. Perutz Laboratories, University of Vienna, Campus Vienna Biocenter, 1030 Vienna, Austria.
authors: Dražen
authors: D
authors: Petrov
authors: Université Pierre et Marie Curie - UPMC, Plateforme d'Interactions Moléculaires, Institut de Biologie Paris-Seine, IBPS, 7 Quai Saint-Bernard, 75252 Paris cedex 05, France.
authors: Tahar
authors: T
authors: Bouceba
authors: Université Pierre et Marie Curie - UPMC, Equipe Biogenèse des signaux peptidiques, ER3, 7 Quai Saint-Bernard, Paris cedex 05, France; Biology of Aquatic Organisms and Ecosystems (BOREA), UMR CNRS 7208 - UPMC - IRD207, Muséum National d'Histoire Naturelle, 7 rue Cuvier, CP32, 75231 Paris cedex 05, France.
authors: Nédia
authors: N
authors: Kamech
authors: Department of Life Sciences, University of Trieste, Via Giorgieri 5, 34127 Trieste, Italy.
authors: Monica
authors: M
authors: Benincasa
authors: Faculty of Science, University of Split, Nikole Tesle 12, 21000 Split, Croatia. Electronic address: juretic@pmfst.hr.
authors: Davor
authors: D
authors: Juretić
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D045744:Cell Line, Tumor; D004269:DNA, Bacterial / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008566:Membranes / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D054909:Placozoa / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance; D020298:U937 Cells
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004269:DNA, Bacterial; D018076:DNA, Complementary
keywords: Antimicrobial peptide; EST database; Peptide–membrane interaction; Selectivity index; Surface plasmon resonance; Trichoplax adhaerens