A NOVEL INDUCIBLE ANTIBACTERIAL PEPTIDE OF DROSOPHILA CARRIES AN O-GLYCOSYLATED SUBSTITUTION

One of the facets of the host defense of higher insects is the rapid a nd transient synthesis, following bacterial challenge or trauma, of a battery of potent antibacterial peptides (Steiner, H., Hultmark, D., E ngstrom, A., Bennich, H., and Boman, H. G. (1981) Nature 292, 246-248) . The best characterized of these peptides are the cecropins (ibid.), 4-kDa peptides devoid of cysteines, and the insect defensins (Hoffmann , J. A., and Hetru, C. (1992) Immunol. Today 13, 411-415), 4-kDa pepti des with three intramolecular disulfide bridges. Several other inducib le antibacterial peptides have been characterized only at the level of their amino acid sequences (Hoffmann, J. A., Dimarcq, J. L., and Bule t, P. (1992) Medecine & Sciences 8, 432-439). We report here the isola tion of a novel 19-residue proline-rich inducible antibacterial peptid e from Drosophila. In contrast to all previous reports on antibacteria l peptides, this molecule carries a substitution as evidenced by molec ular mass determinations; our data show that this reflects the O-glyco sylation of a Thr residue by an N-acetylgalactosamine plus a galactose . A synthetic nonsubstituted peptide of identical amino acid sequence has an activity several times lower (5-10) than the native compound. O ur data suggest that this substitution represents a post-translational modification essential for the full biological activity of this novel peptide.