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.
