The production of antimicrobial peptides and proteins HN1 is an important means of host defense in eukaryotes (1). The larger antimicrobial proteins are often lytic enzymes, nutrient-binding proteins or proteins containing sites that target specific microbial macromolecules. The smaller antimicrobial peptides (defined here as peptides containing fewer than 100 amino acids) act, at least in part, by disrupting the structure or function of microbial cell membranes. In the last 20 years, hundreds of antimicrobial peptides have been found in plants and in the cells and body fluids of multicellular animals, from mollusks to humans. Some antimicrobial peptides are produced constitutively; others are induced in response to infection or inflammation. Studies of the regulation of antimicrobial peptide synthesis in Drosophila have been particularly fruitful, providing new directions for the analysis of mammalian host defense HN2 (2). Although antimicrobial peptides display a variety of shapes and amino acid compositions, many of those found in vertebrates are defensins HN3, 3-to 6-kD β-sheet peptides that contain three disulfides and are encoded by related genes (3). Structurally and functionally similar defensin-like peptides also abound in insects, other invertebrates, and plants. Now, two reports in this issue (4, 5) and a third published 2 weeks ago (6) provide new insights into the biology of vertebrate defensins.

Like most antimicrobial peptides, defensins are cationic (polar) molecules with spatially separated hydrophobic and charged regions. This arrangement allows them to insert themselves into phospholipid HN4 membranes so that their hydrophobic regions are buried within the oily membrane interior and their cationic regions interact with anionic phospholipid head groups and water. In the membrane, some defensins assemble into multimeric pores. Defensins and other antimicrobial peptides preferentially disrupt bacterial membranes that are rich in negatively charged phospholipids. Conversely, the lower anionic phospholipid content of the cell membranes of higher animals may provide relative protection from collateral damage.