APIDAECIN-TYPE PEPTIDE ANTIBIOTICS FUNCTION THROUGH A NON-POREFORMINGMECHANISM INVOLVING STEREOSPECIFICITY

Insect resistance to bacterial infections is dependent on the producti on of specialized defense peptides. We report here that lethal aciviti ties 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 exc eed lethal doses by four orders of magnitude, and undiminished sensiti vity of apidaecin-resistant mutants to 'poreforming' peptides. In addi tion, the D-enantiomer of apidaecin is completely devoid of antibacter ial activities. We propose therefore, that the antagonistic effects of apidaecin involve stereoselective recognition of a chiral cellular ta rget, establishing this peptide as functionally unique among insect an tibacterials. Identification of the apidaecin target may provide the s cientific basis for rational drug design. (C) 1994 Academic Press, Inc .