The Streptococcus pyogenes fibronectin/tenascin-binding protein PrtF.2 contributes to virulence in an influenza

Andrea L Herrera1, Haddy Faal1, Danielle Moss1

  • 1Division of Basic Biomedical Sciences, The Sanford School of Medicine of the University of South Dakota, Vermillion, South Dakota, USA.

Scientific Reports
|August 16, 2018
PubMed

Insights

Influenza A virus and Streptococcus pyogenes coinfections are worsened by tenascin C (TNC). A specific GAS protein, PrtF.2, binds TNC, increasing bacterial virulence and mortality in mice during superinfection.

Area of Science:

  • Microbiology and Virology
  • Immunology
  • Molecular Biology

Background:

  • Viral-bacterial superinfections, particularly involving Influenza A virus (IAV) and Streptococcus pyogenes (Group A Streptococcus; GAS), pose significant health risks.
  • The precise molecular mechanisms underlying these superinfections remain incompletely understood.
  • IAV infection alters host cell gene expression, potentially influencing subsequent bacterial interactions.

Purpose of the Study:

  • To investigate the role of tenascin C (TNC) in IAV-GAS superinfections.
  • To determine if TNC influences the adherence and virulence of GAS during coinfection with IAV.
  • To elucidate the contribution of the GAS fibronectin-binding protein PrtF.2 to superinfection outcomes.

Main Methods:

  • Gene expression analysis in A549 cells following IAV infection to identify upregulated fibronectin type III (FnIII) domain-containing proteins.
  • Creation and characterization of a GAS mutant strain lacking the PrtF.2 protein.
  • In vitro assays to assess GAS co-localization with and binding to TNC, and adherence to IAV-infected cells.
  • In vivo murine model to evaluate the impact of PrtF.2 on GAS abundance in lungs and survival rates after IAV-GAS superinfection.

Main Results:

  • IAV infection increased the expression of TNC in A549 cells.
  • Wild-type GAS, but not the prtF.2 mutant, co-localized with and bound to TNC.
  • Wild-type GAS exhibited enhanced adherence to IAV-infected cells and greater lung abundance compared to the prtF.2 mutant.
  • Mice infected with IAV and the prtF.2 mutant showed significantly higher survival rates than those infected with IAV and wild-type GAS.

Conclusions:

  • Tenascin C (TNC) plays a role in mediating the interaction between GAS and IAV-infected host cells.
  • The fibronectin-binding protein PrtF.2 of GAS is crucial for TNC binding and contributes significantly to GAS virulence during IAV-GAS superinfection.
  • Targeting PrtF.2 may represent a therapeutic strategy to mitigate severe outcomes of IAV-GAS superinfections.

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