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Research Article

The role of antimicrobial peptides in animal defenses

Robert E. W. Hancock and Monisha G. Scott
PNAS August 1, 2000 97 (16) 8856-8861; https://doi.org/10.1073/pnas.97.16.8856
Robert E. W. Hancock
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Monisha G. Scott
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Abstract

It is becoming clear that the cationic antimicrobial peptides are an important component of the innate defenses of all species of life. Such peptides can be constitutively expressed or induced by bacteria or their products. The best peptides have good activities vs. a broad range of bacterial strains, including antibiotic-resistant isolates. They kill very rapidly, do not easily select resistant mutants, are synergistic with conventional antibiotics, other peptides, and lysozyme, and are able to kill bacteria in animal models. It is known that bacterial infections, especially when treated with antibiotics, can lead to the release of bacterial products such as lipopolysaccharide (LPS) and lipoteichoic acid, resulting in potentially lethal sepsis. In contrast to antibiotics, the peptides actually prevent cytokine induction by bacterial products in tissue culture and human blood, and they block the onset of sepsis in mouse models of endotoxemia. Consistent with this, transcriptional gene array experiments using a macrophage cell line demonstrated that a model peptide, CEMA, blocks the expression of many genes whose transcription was induced by LPS. The peptides do this in part by blocking LPS interaction with the serum protein LBP. In addition, CEMA itself has a direct effect on macrophage gene expression. Because cationic antimicrobial peptides are induced by LPS and are able to dampen the septic response of animal cells to LPS, we propose that, in addition to their role in direct and lysozyme-assisted killing of microbes, they have a role in feedback regulation of cytokine responses. We are currently developing variant peptides as therapeutics against antibiotic-resistant infections.

  • Abbreviations

    TNF,
    tumor necrosis factor;
    LPS,
    lipopolysaccharide;
    LTA,
    lipoteichoic acid;
    PG,
    peptidoglycan;
    LPB,
    LPS-binding protein
    • Copyright © 2000, The National Academy of Sciences
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    The role of antimicrobial peptides in animal defenses
    Robert E. W. Hancock, Monisha G. Scott
    Proceedings of the National Academy of Sciences Aug 2000, 97 (16) 8856-8861; DOI: 10.1073/pnas.97.16.8856

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    The role of antimicrobial peptides in animal defenses
    Robert E. W. Hancock, Monisha G. Scott
    Proceedings of the National Academy of Sciences Aug 2000, 97 (16) 8856-8861; DOI: 10.1073/pnas.97.16.8856
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    Proceedings of the National Academy of Sciences: 97 (16)
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    • Article
      • Abstract
      • The Nature of Cationic Antimicrobial Peptides
      • Mechanism of Production in Animals
      • Evidence for Their Role in Host Defenses
      • Mechanism of Action
      • Role in Counteracting Sepsis
      • Peptide/Lysozyme and Peptide/Peptide Synergy
      • Potential as Therapeutics
      • Acknowledgments
      • Footnotes
      • Abbreviations
      • References
    • Figures & SI
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