In this report we study the role of the Amino Terminal Copper- and Nickel- (ATCUN) binding sequence in the peptide Ixosin, isolated from the salivary glands of the hard tick <i>Ixodes sinensis</i>. Our results indicate that the ATCUN motif is indispensable to its oxidative mechanism of action. Specifically, the ATCUN motif promotes lipid (per)oxidation of bacterial membranes in a temporal fashion coinciding with the onset of bacterial death. Microscopy and biophysical studies indicate that the oxidized phospholipids are utilized as potential targets of Ixosin B (another tick salvary gland peptide) involving its delocalization to the bacterial membrane, thus resulting in a synergistic effect. Our proposed mechanism of action highlights the centrality of the ATCUN motif to ixosin’s mechanism of action and demonstrate a novel way in which (tick) AMPs utilize metal ions in its activity. This study suggests that ticks employ a variety of effectors to generate an amplified immune response, possibly justifying its vector competence.

Peptide ixosin uses an ATCUN motif for its oxidative antimicrobial activity and its synergy with other tick peptides

251st National Meeting (2016)

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