APIDAECIN-TYPE PEPTIDE ANTIBIOTICS FUNCTION THROUGH A NON-POREFORMING MECHANISM INVOLVING STEREOSPECIFICITY

Insect resistance to bacterial infections is dependent on the production of specialized defense peptides. We report here that lethal acivitities of apidaecin, a small peptide from honeybees, cannot possibly be the result of a conventional 'lytic' mechanism. Evidence includes the complete lack of membrane permeabilization, at concentrations that exceed lethal doses by four orders of magnitude, and undiminished sensitivity of apidaecin-resistant mutants to 'poreforming' peptides. In addition, the D-enantiomer of apidaecin is completely devoid of antibacterial activities. We propose therefore, that the antagonistic effects of apidaecin involve stereoselective recognition of a chiral cellular target, establishing this peptide as functionally unique among insect antibacterials. Identification of the apidaecin target may provide the scientific basis for rational drug design. (C) 1994 Academic Press, Inc.