Antimicrobial peptides in mammalian and insect host defence

https://doi.org/10.1016/S0952-7915(99)80005-3Get rights and content

Abstract

During the past year, additional insights into systems that regulate antimicrobial peptide production in Drosophila were reported. Granulysin, a peptide stored in the cytoplasmic granules of human natural killer cells and cytolytic T cells, was shown to kill Mycobacterium tuberculosis. More data implicating antimicrobial peptides in the pathogenesis of bronchopulmonary infections in cystic fibrosis appeared. Studies that examined the potential contributions of antimicrobial peptides to regional innate immunity gained in prominence. Efforts to design peptide analogues to prevent or treat infections continued.

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

References (54)

  • I Minn et al.

    Antimicrobial peptides derived from pepsinogens in the stomach of the bullfrog, Rana catesbeiana

    Biochim Biophys Acta

    (1998)
  • EA Levashina et al.

    Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin

    J Mol Biol

    (1998)
  • D Marchini et al.

    Presence of antibacterial peptides on the laid egg chorion of the medfly Ceratitis capitata

    Biochem Biophys Res Commun

    (1997)
  • M Shahabuddin et al.

    Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin

    Exp Parasitol

    (1998)
  • S Taguchi et al.

    A novel insect defensin from the ant Formica rufa

    Biochimie

    (1998)
  • R Maget-Dana et al.

    Penetration of the insect defensin A into phospholipid monolayers and formation of defensin A-lipid complexes

    Biophys J

    (1997)
  • B Ammar et al.

    Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes

    Biochem Biophys Res Commun

    (1998)
  • L Zhang et al.

    Determinants of recombinant production of antimicrobial cationic peptides and creation of peptide variants in bacteria

    Biochem Biophys Res Commun

    (1998)
  • JH Lee et al.

    Acidic peptide-mediated expression of the antimicrobial peptide buforin II as tandem repeats in Escherichia coli

    Protein Expr Purif

    (1998)
  • RE Hancock et al.

    Cationic peptides: a new source of antibiotics

    Trends Biotechnol

    (1998)
  • M Simmaco et al.

    Effect of glucocorticoids on the synthesis of antimicrobial peptides in amphibian skin

    FEBS Lett

    (1997)
  • HG Boman

    Gene-encoded peptide antibiotics and the concept of innate immunity: an update review

    Scand J Immunol

    (1998)
  • M Meister et al.

    Antimicrobial peptide defense in Drosophila

    Bioessays

    (1997)
  • LK Ryan et al.

    Expression of beta-defensin genes in bovine alveolar macrophages

    Infect Immun

    (1998)
  • K Arnljots et al.

    Timing, targeting and sorting of azurophil granule proteins in human myeloid cells

    Leukemia

    (1998)
  • AJ Quayle et al.

    Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract

    Am J Pathol

    (1998)
  • EV Valore et al.

    Human beta-defensin-1: an antimicrobial peptide of urogenital tissues

    J Clin Invest

    (1998)
  • Cited by (668)

    View all citing articles on Scopus
    View full text