Antimicrobial peptides in mammalian and insect host defence
Introduction
The cells of insects and animals produce various antimicrobial substances that act as endogenous antibiotics or disinfectants. This review centers on antimicrobial peptides that contain fewer than about 100 amino acids. Most of these peptides are amphipathic, carry a net positive charge and manifest a well-defined α-helical or β-sheet structure in membrane-like environments. Some antimicrobial peptides are produced by the epithelial cells which line the respiratory, gastrointestinal and genitourinary tracts. Others are found in glandular secretions that moisten and lubricate such surfaces. Antimicrobial peptides may be especially abundant in certain phagocytes — migratory cells that can surround, ingest and kill microbial invaders. Expression of antimicrobial peptides can be constitutive, inducible or both. Several reviews of this topic appeared during the past year [1••, 2••, 3].
Insects and mammals typically express multiple antimicrobial peptides. For example, at least 10 sheep genes encode antimicrobial peptides, including 8 cathelicidins and 2 β-defensins [4]. The bovine genome contains genes for at least 11 cathelicidins [5] and over 20 β-defensins [6].
Section snippets
β-sheet peptides
Mammalian defensins are β-sheet peptides with between 29 and about 40 amino acid residues and 3 intramolecular cysteine-disulfide bonds. The α- and β-defensins differ with respect to the placement and connectivity of their 6 cysteine residues, the structures of their precursors and their patterns of expression. The β-defensin branch of this family is phyletically older than the α-defensin branch.
Antimicrobial peptides in insects
Drosophila responds to septic injury by rapidly synthesizing antimicrobial peptides, predominantly in the fat body which is considered a functional equivalent of the mammalian liver. These peptides are secreted into the hemolymph, where their concentrations can reach 100 μM [2••].
Mechanisms of action of antimicrobial peptides
Magainin, an antimicrobial α-helical peptide from Xenopus laevis skin, has been widely used as a model. It interacts preferentially with phosphatidylglycerol, an abundant acidic phospholipid in bacterial membranes. Magainin imposed positive curvature strain on phosphatidylglycerol-rich model membranes, facilitating formation of a toroidal pore [44]. The resulting peptide–lipid supramolecular complex allowed trans-bilayer traffic of ions, lipids and peptides. This dissipated the transmembrane
Miscellaneous studies
Genetic and biochemical evidence indicated that gonococcal susceptibility to the lethal action of LL-37 and other antimicrobial peptides was modulated by the mtr (multiple transferrable resistance) energy-dependent efflux system [48]. Efficient means of producing recombinant antimicrobial peptides [49, 50•] and an approach for designing antimicrobial peptides based on structural considerations and analogy to known natural sequences have been described [51]. The potential development of
Conclusions
Although progress has been made in delineating how insects regulate the systemic antimicrobial peptide response, we know very little about this in vertebrates. The local and regional antimicrobial peptide expression in tissues has become a fruitful subject of research in insects and mammals but we remain relatively ignorant about antimicrobial molecules in secretions. Many antimicrobial peptides probably remain to be discovered in humans. To date, belief in the functional significance of
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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