Antimicrobial peptides appear to be ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. During the past 15 years a multitude of these peptides have been isolated largely from insects. In spite of great differences in size, amino acid composition and structure, most of the antimicrobial peptides from insects can be grouped into one of three categories. The largest category in number contains peptides with intramolecular disulfide bonds forming hairpin-like β-sheets or α-helical–β-sheet mixed structures. The second most important group is composed of peptides forming amphipathic α-helices. The third group comprises peptides with an overrepresentation in proline and/or glycine residues. In general, the insect antimicrobial peptides have a broad range of activity and are not cytotoxic. Despite a wealth of information on structural requirements for their antimicrobial activity, the mode of action of these peptides is not yet fully understood. However, some data suggest the existence of two types of mode of action: 1. through peptide–lipid interaction or 2. through receptor-mediated recognition processes. This review presents the main results obtained during the last four years in the field of antimicrobial peptides from insects with a special focus on the proline-rich and cysteine-rich peptides.

Antimicrobial peptides in insects; structure and function

Antibiotic peptides are a key component of the innate immune systems of most multicellular organisms. Despite broad divergences in sequence and taxonomy, most antibiotic peptides share a common mechanism of action, i.e., membrane permeabilization of the pathogen. This review provides a general introduction to the subject, with emphasis on aspects such as structural types, post-translational modifications, mode of action or mechanisms of resistance. Some of these questions are treated in depth in other reviews in this issue. The review also discusses the role of antimicrobial peptides in nature, including several pathological conditions, as well as recent accounts of their application at the preclinical level.

Animal antimicrobial peptides: an overview.

Host defense peptides are widely distributed in nature, being found in species from bacteria to humans. The structures of these peptides from insects, horseshoe crabs, frogs, and mammals are known to have the common features of a net cationic charge due to the presence of multiple Arg and Lys residues and in most cases the ability to form amphipathic structures. These properties are important for the mechanism of action that is thought to be a nonreceptor-mediated interaction with the anionic phospholipids of the target cell followed by incorporation into the membrane and disruption of the membrane structure. Host defense peptides have been shown to have broad spectrum antimicrobial activity, able to kill most strains of bacteria as well as some fungi, protozoa, and in addition, many types of tumor cells. Specificity for pathogenic cells over host cells is thought to be due to the composition of the cell membranes, with an increased proportion of anionic phospholipids making the pathogen more susceptible and the presence of cholesterol making the host membranes more resistant. Structure-activity relationship studies have been performed on insect cecropins and apidaecins, horseshoe crab tachyplesins and polyphemusins, and the frog magainins, CPFs (caerulein precursor fragments) and PGLa. In general, changes that increased the basicity and stabilized the amphipathic structure have increased the antimicrobial activity; however, as the peptides become more hydrophobic the degree of specificity decreases. One magainin-2 analogue, MSI-78, has been developed by Magainin Pharmaceuticals as a topical antiinfective and is presently in clinical trials for the treatment of infected diabetic foot ulcers.

Structure-activity studies on magainins and other host defense peptides.

Amphibian skin secretions contain many biologically active compounds, such as biogenic amines, complex alkaloids, or peptides. Within the latter class of molecules, a large number of peptide antibiotics has been isolated and characterized from different amphibian species. Antimicrobial peptides are considered the effector molecules of innate immunity, acting as a first line of defense against bacterial infections, by perturbing the phospholipid bilayer of the target cell membrane. These gene-encoded molecules are synthesized as inactive precursors and in several cases their proparts were shown to have highly conserved structures. It has also been demonstrated that the promoter regions of inducible peptide antibiotics are often regulated by the transcriptional control machinery NF-κB/IκBα. In amphibia of Rana and Bombina genera, inhibition of transcription of the genes encoding antimicrobial peptides has been obtained by glucocorticoid treatment, which causes an increase of IκBα synthesis. Moreover, determination of the structure of a number of genes coding for antimicrobial peptides in amphibia has actually shown that their promoter regions contain recognition sites for nuclear factors. © 1999 John Wiley & Sons, Inc. Biopoly 47: 435–450, 1998

Antimicrobial peptides from amphibian skin: what do they tell us?

Antimicrobial peptides from ranid frogs: taxonomic and phylogenetic markers and a potential source of new therapeutic agents.

Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa.

http://link.springer.com/content/pdf/10.1007/978-94-011-1474-5_174.pdf

Noriyuki Morikawa

Papers

Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa.

Isolation and structural characterization of antimicrobial peptides from the skin of frog, Rana brevipoda porsa