Structural and Antimicrobial Features of Peptides Related to Myticin C, a Special Defense Molecule from the Mediterranean Mussel Mytilus galloprovincialis

Mussels (Mytilus spp.) have a large repertoire of cysteine-stabilized α,β peptides, and myticin C (MytC) was identified in some hundreds of transcript variants after in vivo immunostimulation. Using a sequence expressed in Italian mussels, we computed the MytC structure and synthesized the mature MytC and related peptide fragments (some of them also prepared in oxidized form) to accurately assess their antibacterial and antifungal activity. Only when tested at pH 5 was the reduced MytC as well as reduced and oxidized fragments including structural β-elements able to inhibit Gram-positive and -negative bacteria (MIC ranges of 4–32 and 8–32 μM, respectively). Such fragments caused selective Escherichia coli killing (MBC of 8–32 μM) but scarcely inhibited two fungal strains. In detail, the antimicrobial β-hairpin MytC[19–40]­S_OX caused membrane-disrupting effects in <i>E. coli</i> despite its partially ordered conformation in membrane-mimetic environments. In perspective, MytC-derived peptides could be employed to protect acidic mucosal tissues, in cosmetic and food products, and, possibly, as adjuvants in aquaculture