Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence

Biol Chem. 2011 May;392(5):483-9. doi: 10.1515/BC.2011.044.


Bacterial proteases are considered virulence factors and it is presumed that by abrogating their activity, host endogenous protease inhibitors play a role in host defense against invading pathogens. Here we present data showing that Staphylococcus aureus cysteine proteases (staphopains) are efficiently inhibited by Squamous Cell Carcinoma Antigen 1 (SCCA1), an epithelial-derived serpin. The high association rate constant (k(ass)) for inhibitory complex formation (1.9×10(4) m/s and 5.8×10(4) m/s for staphopain A and staphopain B interaction with SCCA1, respectively), strongly suggests that SCCA1 can regulate staphopain activity in vivo at epithelial surfaces infected/colonized by S. aureus. The mechanism of staphopain inhibition by SCCA1 is apparently the same for serpin interaction with target serine proteases whereby the formation of a covalent complex result in cleavage of the inhibitory reactive site peptide bond and associated release of the C-terminal serpin fragment. Interestingly, the SCCA1 reactive site closely resembles a motif in the reactive site loop of native S. aureus-derived inhibitors of the staphopains (staphostatins). Given that S. aureus is a major pathogen of epithelial surfaces, we suggest that SCCA1 functions to temper the virulence of this bacterium by inhibiting the staphopains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Antigens, Neoplasm / pharmacology*
  • Blotting, Western
  • Cysteine Endopeptidases / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation / drug effects
  • Humans
  • Protein Binding
  • Serpins / metabolism
  • Serpins / pharmacology*


  • Antigens, Neoplasm
  • Serpins
  • squamous cell carcinoma-related antigen
  • Cysteine Endopeptidases
  • staphopain A protein, Staphylococcus aureus
  • staphopain B protein, Staphylococcus aureus