Comparison of the action of different proteases on virulence properties related to the staphylococcal surface

J Appl Microbiol. 2013 Jan;114(1):266-77. doi: 10.1111/jam.12038. Epub 2012 Nov 19.


Aims: The purpose of this study was to evaluate the antimicrobial efficacy of five different proteases belonging to two different families on Staphylococcus aureus and Staphylococcus epidermidis strains.

Methods and results: We used three serine proteases and two metalloproteases in single species biofilm formation assays and in human cell invasion processes. Following each protease incubation with bacterial cells, surface protein patterns were analysed by SDS-PAGE and zymography. Some differently expressed proteins were identified by mass spectrometry.

Conclusions: The effect of tested proteases on biofilm formation was not related to the protease category but was strain-dependent and was related to the biofilm formation capacity of each staphylococcal strain. Some proteases showed a nonspecific and indiscriminate effect on surface proteins, while others induced a discrete and reproducible action on protein profiles.

Significance and impact of the study: The inhibition of the surface-related virulence factors is a promising avenue to overcome persistent infections caused by bacterial biofilms. To this end, we show here that proteases, in particular the metalloprotease serratiopeptidase, can interfere with adhesion and invasion of eukaryotic cells and biofilm formation in staphylococci and their use could represent a viable treatment for the development of novel combination therapies.

Publication types

  • Comparative Study

MeSH terms

  • Bacterial Adhesion
  • Bacterial Proteins / analysis
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Genes, Bacterial
  • HeLa Cells
  • Humans
  • Membrane Proteins / analysis
  • Metalloproteases / pharmacology*
  • Peptide Hydrolases / pharmacology
  • Serine Proteases / pharmacology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / pathogenicity*
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / genetics
  • Staphylococcus epidermidis / pathogenicity*
  • Virulence


  • Bacterial Proteins
  • Membrane Proteins
  • Metalloproteases
  • Peptide Hydrolases
  • Serine Proteases
  • serratiopeptidase