Tyrosine tRNA synthetase as a novel extracellular immunomodulatory protein in Streptococcus anginosus

FEMS Microbiol Lett. 2020 Sep 25;367(18):fnaa153. doi: 10.1093/femsle/fnaa153.

Abstract

Streptococcus anginosus is frequently detected in patients with infective endocarditis, abscesses or oral cancer. Although S. anginosus is considered the causative pathogen of these diseases, the pathogenic mechanisms of the bacterium have remained unclear. Previously, we suggested that an extracellular antigen from S. anginosus (SAA) serves as a pathogenic factor by inducing nitric oxide production in murine macrophages. In the present study, we identified SAA using LC-MS/MS and assessed the biological activities of His-tagged recombinant SAA in murine macrophages. SAA was identified as a tyrosine tRNA synthetase (SaTyrRS) that was isolated from the extracellular fraction of S. anginosus but not from other oral streptococci. In addition, inducible nitric oxide synthase and TNF-α mRNA expression was induced in recombinant SaTyrRS-stimulated murine macrophages. However, their mRNA expression was not induced in macrophages stimulated with truncated or heat-inactivated recombinant SaTyrRS, and the activation motif was identified as Arg264-Thr270. Consequently, these results indicated that SaTyrRS could be a novel and specific immunomodulatory protein in S. anginosus.

Keywords: Streptococcus; aminoacyl-tRNA synthetase; bacterial pathogenesis; inflammation; nitric oxide synthetase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Cell Line
  • Extracellular Space / metabolism
  • Humans
  • Inflammation
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Streptococcal Infections / microbiology
  • Streptococcus anginosus / enzymology
  • Streptococcus anginosus / isolation & purification
  • Streptococcus anginosus / pathogenicity*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tyrosine-tRNA Ligase / chemistry
  • Tyrosine-tRNA Ligase / genetics
  • Tyrosine-tRNA Ligase / immunology*
  • Tyrosine-tRNA Ligase / metabolism
  • Virulence Factors / chemistry
  • Virulence Factors / genetics
  • Virulence Factors / immunology*
  • Virulence Factors / metabolism

Substances

  • Antigens, Bacterial
  • Recombinant Proteins
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • Virulence Factors
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Tyrosine-tRNA Ligase