Apidaecin-Type Peptide Antibiotics Function through a Nonporeforming Mechanism Involving Stereospecificity

Abstract

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. © 1994 Academic Press. All rights reserved.