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Staphylococcal SplA and SplB serine proteases target ubiquitin(-like) specific proteases

Felix L Glinka1, Ole Schmöker2, Abhishek K Singh3

  • 1Department of Biotechnology & Enzyme Catalysis, Institute of Biochemistry, University of Greifswald, Greifswald, Germany.

AMB Express
|February 22, 2025
PubMed

Insights

Staphylococcus aureus serine proteases (Spls) cleave ubiquitin-modifying enzymes, potentially disrupting host immune signaling. This study identifies novel substrates and cleavage sites for SplA and SplB, offering insights into bacterial pathogenesis.

Area of Science:

  • Microbiology
  • Biochemistry
  • Immunology

Background:

  • Staphylococcus aureus is a common human pathogen causing severe infections.
  • Extracellular serine protease-like proteins (Spls) are virulence factors of S. aureus with unknown functions.
  • Understanding Spl substrates is crucial for elucidating their role in infection.

Purpose of the Study:

  • To characterize the substrate and cleavage specificity of SplA and SplB.
  • To identify novel pathophysiological substrates of S. aureus Spls.
  • To investigate the role of Spls in manipulating host immune responses.

Main Methods:

  • Recombinant expression and purification of SplA and SplB proteins.
  • Mass spectrometry-based substrate identification and cleavage site mapping.
  • Site-directed mutagenesis to confirm cleavage sites in target proteins.

Main Results:

  • Identified ubiquitin or ubiquitin-like modifying enzymes as novel substrates for SplA and SplB.
  • Determined distinct cleavage sites for SplA (YLY↓T, FMY↓N) and SplB (VCD↓S).
  • Demonstrated that Spls cleave key components of ubiquitination pathways.

Conclusions:

  • SplA and SplB specifically cleave ubiquitin-modifying enzymes, including deubiquitinating enzymes.
  • This cleavage activity suggests a mechanism for S. aureus to manipulate host immune signaling.
  • Spls may play a role in bacterial competition and pathogenesis by targeting immune pathways.
Keywords:
Staphylococcus aureusDeubiquitinationProtein degradationSerine protease-likeSplASplB

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