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Updated: Feb 6, 2026

Purification of a High Molecular Mass Protein in Streptococcus mutans
Published on: September 14, 2019
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.
Abstract:
Influenza A virus (IAV) and Streptococcus pyogenes (the group A Streptococcus; GAS) are important contributors to viral-bacterial superinfections, which result from incompletely defined mechanisms. We identified changes in gene expression following IAV infection of A549 cells. Changes included an increase in transcripts encoding proteins with fibronectin-type III (FnIII) domains, such as fibronectin (Fn), tenascin N (TNN), and tenascin C (TNC). We tested the idea that increased expression of TNC may affect the outcome of an IAV-GAS superinfection. To do so, we created a GAS strain that lacked the Fn-binding protein PrtF.2. We found that the wild-type GAS strain, but not the mutant, co-localized with TNC and bound to purified TNC. In addition, adherence of the wild-type strain to IAV-infected A549 cells was greater compared to the prtF.2 mutant. The wild-type strain was also more abundant in the lungs of mice 24 hours after superinfection compared to the mutant strain. Finally, all mice infected with IAV and the prtF.2 mutant strain survived superinfection compared to only 42% infected with IAV and the parental GAS strain, indicating that PrtF.2 contributes to virulence in a murine model of IAV-GAS superinfection.
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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