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

Tomasz Kantyka, Karolina Plaza, Joanna Koziel, Danuta Florczyk, Hennig R. Stennicke, Ida B. Thogersen, Jan J. Enghild, Gary A. Silverman, Stephen C. Pak, Jan Potempa

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 (kass) for inhibitory complex formation (1.9×104 m/s and 5.8×104 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.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
JournalBiological Chemistry
Volume392
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • cathepsin-like protease
  • inhibition
  • pathogenicity
  • proteolysis regulation
  • serpin
  • staphylococcal infection
  • virulence factor

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