A method based on the use of signal peptide sequences fromantimicrobial peptide (AMP) precursorswas 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 á-helical structure in contact with membrane-like environments and is active against both Gram-negative and Gram-positive bacterial species (includingMRSA), as well as yeasts from the Candida genus. The cytotoxic activity, as assessed by the haemolytic activity against rat erythrocytes, U937 cell permeabilization to propidiumiodide andMCF7 cellmitochondrial activity, is significantly lower than the antimicrobial activity. In tests with membrane models, trichoplaxin shows high affinity for anionic prokaryote-likemembraneswith good fit in kinetic studies. Conversely, there is a lowaffinity 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.

Trichoplaxin - A new membrane-active antimicrobial peptide from placozoan cDNA

BENINCASA, MONICA;
2014

Abstract

A method based on the use of signal peptide sequences fromantimicrobial peptide (AMP) precursorswas 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 á-helical structure in contact with membrane-like environments and is active against both Gram-negative and Gram-positive bacterial species (includingMRSA), as well as yeasts from the Candida genus. The cytotoxic activity, as assessed by the haemolytic activity against rat erythrocytes, U937 cell permeabilization to propidiumiodide andMCF7 cellmitochondrial activity, is significantly lower than the antimicrobial activity. In tests with membrane models, trichoplaxin shows high affinity for anionic prokaryote-likemembraneswith good fit in kinetic studies. Conversely, there is a lowaffinity 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2870843
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