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Staphylococcus aureus virulence attenuation and immune clearance mediated by a phage lysin-derived protein

Hang Yang1, Jingjing Xu2, Wuyou Li2

  • 1Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

The EMBO Journal
|July 25, 2018
PubMed

Insights

A novel protein, V12CBD, combats multi-drug-resistant Staphylococcus aureus (MRSA) by reducing its virulence and boosting immune responses. This bacteriophage-derived molecule offers a promising new strategy against dangerous bacterial infections.

Area of Science:

  • Microbiology
  • Immunology
  • Biotechnology

Background:

  • Multi-drug-resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), pose a significant global health threat.
  • Novel anti-infective strategies are urgently required to overcome the limitations of current treatments.

Purpose of the Study:

  • To investigate the potential of V12CBD, a recombinant protein from bacteriophage lysin PlyV12's cell wall binding domain (CBD), as a novel anti-infective agent.
  • To evaluate V12CBD's effects on Staphylococcus aureus virulence and host immune system modulation.

Main Methods:

  • Characterization of V12CBD's interaction with Staphylococcus aureus.
  • Assessment of V12CBD's impact on bacterial invasion of epithelial cells and susceptibility to macrophage killing.
  • Quantification of virulence gene expression in Staphylococcus aureus following V12CBD treatment.
  • Analysis of V12CBD's effect on macrophage activation via the NF-κB pathway and phagocytosis.
  • Evaluation of V12CBD's efficacy in murine models of MRSA infection (therapeutic and prophylactic).

Main Results:

  • V12CBD binding reduced Staphylococcus aureus invasion of epithelial cells and increased susceptibility to macrophage-mediated killing.
  • V12CBD significantly downregulated the expression of key Staphylococcus aureus virulence genes (2.4- to 23.4-fold).
  • V12CBD activated macrophages through the NF-κB pathway, enhancing their phagocytic capacity against Staphylococcus aureus.
  • V12CBD demonstrated protective effects in both therapeutic and prophylactic mouse models against MRSA infection.

Conclusions:

  • V12CBD exhibits multifaceted anti-virulence and immunomodulatory properties against Staphylococcus aureus.
  • V12CBD represents a promising novel therapeutic candidate for controlling multi-drug-resistant Staphylococcus aureus infections.
  • The unique mechanisms of V12CBD suggest its potential as an alternative molecule in combating MDR pathogens.
Keywords:
anti‐virulence therapybacteriophage lysincell wall binding domainimmune clearancemacrophage activation

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