PtpA, a secreted tyrosine phosphatase from Staphylococcus aureus, contributes to virulence and interacts with coronin-1A during infection

J Biol Chem. 2018 Oct 5;293(40):15569-15580. doi: 10.1074/jbc.RA118.003555. Epub 2018 Aug 21.

Abstract

Secretion of bacterial signaling proteins and adaptation to the host, especially during infection, are processes that are often linked in pathogenic bacteria. The human pathogen Staphylococcus aureus is equipped with a large arsenal of immune-modulating factors, allowing it to either subvert the host immune response or to create permissive niches for its survival. Recently, we showed that one of the low-molecular-weight protein tyrosine phosphatases produced by S. aureus, PtpA, is secreted during growth. Here, we report that deletion of ptpA in S. aureus affects intramacrophage survival and infectivity. We also observed that PtpA is secreted during macrophage infection. Immunoprecipitation assays identified several host proteins as putative intracellular binding partners for PtpA, including coronin-1A, a cytoskeleton-associated protein that is implicated in a variety of cellular processes. Of note, we demonstrated that coronin-1A is phosphorylated on tyrosine residues upon S. aureus infection and that its phosphorylation profile is linked to PtpA expression. Our results confirm that PtpA has a critical role during infection as a bacterial effector protein that counteracts host defenses.

Keywords: Staphylococcus aureus (S. aureus); bacterial pathogenesis; bacterial protein phosphatase; coronin; host-pathogen interaction; protein phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Cloning, Molecular
  • Dictyostelium / genetics
  • Dictyostelium / metabolism
  • Female
  • Gene Expression
  • Gene Expression Regulation
  • Host-Pathogen Interactions*
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • RAW 264.7 Cells
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Staphylococcal Infections / genetics*
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / pathogenicity
  • Tyrosine / metabolism
  • Virulence

Substances

  • Bacterial Proteins
  • Microfilament Proteins
  • Recombinant Proteins
  • coronin proteins
  • Tyrosine
  • Protein Tyrosine Phosphatases