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 activities 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.
Casteels
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P
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY.
Tempst
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P
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D023181:Antimicrobial Cationic Peptides; D002463:Cell Membrane Permeability / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000633:toxicity*; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C061361:apidaecin