The antibacterial and antifungal properties of trappin-2 (pre-elafin) do not depend on its protease inhibitory function

FEBS J. 2008 May;275(9):2008-20. doi: 10.1111/j.1742-4658.2008.06355.x. Epub 2008 Mar 13.


Trappin-2 (also known as pre-elafin) is an endogenous inhibitor of neutrophil serine proteases and is involved in the control of excess proteolysis, especially in inflammatory events, along with the structurally related secretory leucocyte proteinase inhibitor. Secretory leucocyte proteinase inhibitor has been shown to have antibacterial and antifungal properties, whereas recent data indicate that trappin-2 has antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In the present study, we tested the antibacterial properties of trappin-2 towards other respiratory pathogens. We found that trappin-2, at concentrations of 5-20 microm, has significant activity against Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis and the pathogenic fungi Aspergillus fumigatus and Candida albicans, in addition to P. aeruginosa and S. aureus. A similar antimicrobial activity was observed with trappin-2 A62D/M63L, a trappin-2 variant that has lost its antiprotease properties, indicating that trappin-2 exerts its antibacterial effects through mechanisms independent from its intrinsic antiprotease capacity. Furthermore, the antibacterial and antifungal activities of trappin-2 were sensitive to NaCl and heparin, demonstrating that its mechanism of action is most probably dependent on its cationic nature. This enables trappin-2 to interact with the membranes of target organisms and disrupt them, as shown by our scanning electron microscopy analyses. Thus, trappin-2 not only provides an antiprotease shield, but also may play an important role in the innate defense of the human lungs and mucosae against pathogenic microorganisms.

MeSH terms

  • Anti-Bacterial Agents / metabolism*
  • Antifungal Agents / metabolism*
  • Disulfides / chemistry
  • Dose-Response Relationship, Drug
  • Elafin / metabolism*
  • Elafin / pharmacology
  • Fibronectins / metabolism
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / ultrastructure
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / ultrastructure
  • Heparin / pharmacology
  • Kinetics
  • Models, Chemical
  • Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / metabolism
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / isolation & purification
  • Serine Proteinase Inhibitors / metabolism*
  • Sodium Chloride / pharmacology


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Disulfides
  • Elafin
  • Fibronectins
  • PI3 protein, human
  • Recombinant Proteins
  • Serine Proteinase Inhibitors
  • Sodium Chloride
  • Heparin
  • Serine Endopeptidases