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Human defensins

Abstract

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free α-helices, extended cysteine-free α-helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and β-sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the α-defensins, β-defensins and the recently described θ-defensins. Mammalian α-defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian β-defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human β-defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known β-defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.

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Acknowledgements

We thank Heinrich Sticht, Bayreuth University, for providing graphics of defensin structures.

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Correspondence to Josef Johann Schneider.

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J.J. Schneider and A. Unholzer contributed equally to this work

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Schneider, J.J., Unholzer, A., Schaller, M. et al. Human defensins. J Mol Med 83, 587–595 (2005). https://doi.org/10.1007/s00109-005-0657-1

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Keywords

  • Antimicrobial peptides
  • Human defensins
  • Human neutrophil peptides
  • HBD-3
  • HBD-4