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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
08:32

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus

Published on: January 17, 2025

Extracellular proteases are key mediators of Staphylococcus aureus virulence via the global modulation of

Stacey L Kolar1, J Antonio Ibarra, Frances E Rivera

  • 1Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.

Microbiologyopen
|December 13, 2012
PubMed

Insights

Extracellular proteases are crucial for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) survival and virulence. Deleting these proteases impairs growth and immune evasion but paradoxically increases mortality in mouse models.

Area of Science:

  • Microbiology and Infectious Diseases
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Staphylococcus aureus is a significant human pathogen responsible for various infections.
  • Community-associated methicillin-resistant S. aureus (CA-MRSA) strains exhibit increased virulence.
  • The role of secreted proteases in CA-MRSA pathogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the contribution of extracellular proteases to CA-MRSA pathogenesis.
  • To elucidate the mechanisms underlying enhanced CA-MRSA virulence.
  • To analyze the impact of exo-protease deletion on bacterial survival and host-pathogen interactions.

Main Methods:

  • Construction and characterization of a CA-MRSA mutant lacking all 10 extracellular proteases.
  • Assessment of bacterial growth in various nutrient-rich environments and human biological fluids.
  • Evaluation of resistance to antimicrobial peptides and phagocytosis by human leukocytes.
  • Murine infection models to assess morbidity and mortality.
  • Proteomic analysis to identify changes in virulence factor abundance.

Main Results:

  • Extracellular proteases are essential for CA-MRSA growth in peptide-rich media, serum, and human blood.
  • Protease-deficient CA-MRSA exhibits impaired resistance to antimicrobial peptides and reduced phagocytosis.
  • Deletion of exo-proteases led to decreased abscess formation and organ invasion in mice.
  • Paradoxically, the protease-null strain exhibited hypervirulence, causing increased mortality in a murine model.
  • Proteomic analysis revealed that exo-proteases mediate the stability of key secreted and surface-associated virulence proteins.

Conclusions:

  • Extracellular proteases play a dual role in CA-MRSA pathogenesis, influencing both bacterial survival and host immune evasion.
  • The absence of exo-proteases leads to increased stability of virulence factors, contributing to hypervirulence and mortality.
  • These findings offer critical insights into CA-MRSA infection dynamics and the function of secreted proteolytic enzymes.

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