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. alpha-helices or beta-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.