Baicalin promotes the bacteriostatic activity of lysozyme on S. aureus in mammary glands and neutrophilic granulocytes in mice

Oncotarget. 2017 Mar 21;8(12):19894-19901. doi: 10.18632/oncotarget.15193.

Abstract

Staphylococcus aureus causes mastitis as a result of community-acquired or nosocomial infections. Lysozyme (LYSO) is an enzyme that is upregulated in many organisms during the innate immune response against infection by bacterial pathogens. Baicalin is a bioactive flavonoid that can bind to enzymes, often to potentiate their effect. Here we tested the effects of baicalin on the activity of LYSO using the S. aureus mastitis mouse model and neutrophilic granulocyte model of S. aureus infection. In our experiments, S. aureus counts decreased with increasing baicalin concentration. Furthermore, qPCR and western blot analyses showed that LYSO expression was unaffected by baicalin, while fluorescence quenching and UV fluorescence spectral analyses showed that baicalin binds to LYSO. To test whether this binding increased LYSO activity, we assessed LYSO-induced bacteriostasis in the presence of baicalin. Our results showed that LYSO-induced S. aureus bacteriostasis increased with increasing concentrations of baicalin, and that baicalin binding to LYSO synergistically increased the antibacterial activity of LYSO. These results demonstrate that baicalin enhances LYSO-induced bacteriostasis during the innate immune response to S. aureus. They suggest baicalin is a potentially useful therapeutic agent for the treatment of bacterial infections.

Keywords: S. aureus; bacteriostasis; baicalin; lysozyme; mastitis.

MeSH terms

  • Animals
  • Anti-Infective Agents / metabolism
  • Anti-Infective Agents / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Female
  • Flavonoids / metabolism
  • Flavonoids / pharmacology*
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / immunology
  • Mammary Glands, Animal / microbiology
  • Mastitis / immunology
  • Mastitis / microbiology
  • Mastitis / prevention & control
  • Mice, Inbred BALB C
  • Microbial Viability / drug effects
  • Microbial Viability / immunology
  • Muramidase / genetics
  • Muramidase / immunology
  • Muramidase / metabolism*
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / microbiology
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Fluorescence
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / physiology

Substances

  • Anti-Infective Agents
  • Flavonoids
  • baicalin
  • Muramidase