LEHRER, R.I.*; TINCU, J.A.; TAYLOR, S.W.; MENZEL, L.P.; ORLOV, D.S.; WARING, A.J.: Natural peptide antibiotics from tunicates: Structures, functions, and potential uses.

Tunicates rely on hemocyte-mediated innate immunity for protection against microbial and eukaroytic invaders. The hemocytes of Styela clava, a solitary ascidian, include granular, paucigranular and agranular cell types that act as phagocytes, cytotoxic effectors and sources of antimicrobial molecules. At least two families of antimicrobial peptides exist in S. clava hemocytes. Styelins are phenylalanine-rich, 32 residue (3.7 kDa) peptides with broad-spectrum antimicrobial activity. They kill marine bacteria and many human pathogens, often acting at concentrations below 2 micrograms/ml. Styelin D contains many modified amino acids, including hydroxylated lysines and arginines, 6-bromotryptophan and 3,4-dihydroxyphenylalanine. Clavanins, histidine-rich peptides with 23 amino acid residues, are C-terminally amidated and most effective at acidic pH. Clavaspirin is a newly described member of the clavanin family with potent cytotoxic properties. Clavanins are found in the granules of several hemocyte types, and in the cytoplasm of the monocyte-like, agranular hemocytes. The hemocytes of Styela plicata contain plicatamide (Tincu JA,et al., BBRC, 2000, 270:421-424), a modified octapeptide whose primary sequence is Phe-Phe-His-Leu-His- Phe-His-decarboxyDeltaDOPA. Plicatamide, which is unusually small for an antimicrobial peptide, has impressive activity against S. aureus and MRSA and acts via an unusual mechanism.