Antibacterial peptides isolated from insects

• Published in: Journal of peptide science Vol. 6; no. 10; pp. 497 - 511
• Main Author: Otvos, Jr, Laszlo
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2000
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial peptides; Bacteria - drug effects; Escherichia coli; Gene Expression Regulation; insect peptides; Insect Proteins - chemistry; Insect Proteins - isolation & purification; Insect Proteins - pharmacology; Insecta - chemistry; insects; Molecular Sequence Data; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Protein Conformation
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/1099-1387(200010)6:10<497::AID-PSC277>3.0.CO;2-W

Insects are amazingly resistant to bacterial infections. To combat pathogens, insects rely on cellular and humoral mechanisms, innate immunity being dominant in the latter category. Upon detection of bacteria, a complex genetic cascade is activated, which ultimately results in the synthesis of a battery of antibacterial peptides and their release into the haemolymph. The peptides are usually basic in character and are composed of 20–40 amino acid residues, although some smaller proteins are also included in the antimicrobial repertoire. While the proline‐rich peptides and the glycine‐rich peptides are predominantly active against Gram‐negative strains, the defensins selectively kill Gram‐positive bacteria and the cecropins are active against both types. The insect antibacterial peptides are very potent: their IC50 (50% of the bacterial growth inhibition) hovers in the submicromolar or low micromolar range. The majority of the peptides act through disintegrating the bacterial membrane or interfering with membrane assembly, with the exception of drosocin, apidaecin and pyrrhocoricin which appear to deactivate a bacterial protein in a stereospecific manner. In accordance with their biological function, the membrane‐active peptides form ordered structures, e.g. α‐helices or β‐pleated sheets and often cast permeable ion‐pores. Their cytotoxic properties were exploited in in vivo studies targeting tumour progression. Although the native peptides degrade quickly in biological fluids other than insect haemolymph, structural modifications render the peptides resistant against proteases without sacrificing biological activity. Indeed, a pyrrhocoricin analogue shows lack of toxicity in vitro and in vivo and protects mice against experimental Escherichia coli infection. Careful selection of lead molecules based on the insect antibacterial peptides may extend their utility and produce viable alternatives to the conventional antimicrobial compounds for mammalian therapy. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.