Isolation and Characterization of Human μ-Defensin-3, a Novel Human Inducible Peptide Antibiotic

We report the discovery of a novel human epithelial broad spectrum and multiresistant bacteria-killing peptide antibiotic, which we termed human ␤-defensin-3 and which is inducibly expressed by various human epithelial cells

Jürgen Harder; Joachim Bartels; Enno Christophers; Jens-Michael Schröder

2002

Scholarcy highlights

  • Epithelia of macroorganisms represent the first barrier against invading microorganisms
  • We report the discovery of a novel human epithelial broad spectrum and multiresistant bacteria-killing peptide antibiotic, which we termed human ␤-defensin-3 and which is inducibly expressed by various human epithelial cells
  • NH2-terminal amino acid sequence analyses gave the sequence shown in Fig. 1D, which indicated a new human antimicrobial peptide
  • It has been previously demonstrated that the epithelia of plants, insects, amphibians, and several mammals are protected from bacterial infection by a chemical defense shield
  • Our previous observation that hBD-2 is not bactericidal toward S. aureus prompted us to investigate human skin extracts for S. aureuskilling factor(s). These analyses have led to the purification of a novel peptide antibiotic, which we identified as hBD-3
  • A very recent data bank search indicated that, upon sequencing of human chromosome 8 bacterial artificial chromosomes, the hBD-3 gene was identified 15,000 base pairs distant from the hBD-2 gene, further supporting the idea that all human ␤-defensins are clustered on chromosome 8
  • The discovery of this human inducible, epithelial antimicrobial peptide may prove to be a vital advance in dealing with skin and respiratory tract infections and in the development of novel strategies for antimicrobial therapy, i.e. by artificial stimulation of epithelial peptide antibiotic synthesis, as recently shown with the amino acid 1-isoleucin

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