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

By J. Harder, J. Bartels, E. Christophers, J. Schröder. Journal of Biological Chemistry, 2001

1,378 citations recorded by the source corpus.

The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particularStaphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human β-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureusrevealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor α and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.

Subfields: Immunology, Microbiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3e4b7453ce2b032f82cd414b8d1e898c700020ea

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Citations in the corpus

Cytokine Milieu of Atopic Dermatitis, as Compared to Psoriasis, Skin Prevents Induction of Innate Immune Response Genes 1 (2003, methodology): “The U-95Av2 GeneChip Affymetrix probe array that was used in this study did not include a probe for HBD-3 which is a newly identified antimicrobial peptide that has been found to be active against a broad spectrum of microbes (12, 13).”
DNAWorks: an automated method for designing oligonucleotides for PCR-based gene synthesis. (2002, methodology): “Amino acid sequences for the following proteins were obtained from GenBank: human CC-chemokine CCL27, also known as CTACK/ALP/ILC (hCCL27) (8–11), viral interleukin-8 (vIL-8) (12), lettuce mosaic virus protease (LPP) (13), potato virus A protease (PPP) (14), murine monocyte chemoattractant protein-5”
Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system (2004, background): “Both peptides have been shown previously to be active when synthesized by conventional solid-phase synthesis (Harder et al., 2001; Schittek et al., 2001).”
Mammalian defensins in the antimicrobial immune response (2005, background): “Two additional β-defensins, hBD-2 and hBD-3, were subsequently isolated from the scales of psoriatic ski”
Mechanisms and consequences of bacterial resistance to antimicrobial peptides. (2016, background): “Antibacterial activity (direct) Human cathelicidin and human defensins have the capacity to kill a wide variety of Gram-positive and Gram-negative bacteria in vitro (Ganz et al., 1985; Garcia et al., 2001b; Harder et al., 2001, 1997; Ouellette and Selsted, 1996; Zaiou et al., 2003).”