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Characterization of Inflammatory Responses During Intranasal Colonization with Streptococcus pneumoniae
Published on: January 17, 2014
Contribution of Streptococcus pyogenes M87 protein to innate immune resistance and virulence
Yujiro Hirose1, Piotr Kolesinski2, Masanobu Hiraoka3
1Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, 5650871, Japan; Department of Pediatrics, University of California at San Diego, La Jolla, CA, 92093, USA.
Abstract:
Streptococcus pyogenes is a pre-eminent human pathogen, and classified by the hypervariable sequence of the emm gene encoding the cell surface M protein. Among a diversity of M/emm types, the prevalence of the M/emm87 strain has been steadily increasing in invasive S. pyogenes infections. Although M protein is the major virulence factor for globally disseminated M/emm1 strain, it is unclear if or how the corresponding M protein of M/emm87 strain (M87 protein) functions as a virulence factor. Here, we use targeted mutagenesis to show that the M87 protein contributes to bacterial resistance to neutrophil and whole blood killing and promotes the release of mature IL-1β from macrophages. While deletion of emm87 did not influence epithelial cell adherence and nasal colonization, it significantly reduced S. pyogenes-induced mortality and bacterial loads in a murine systemic infection model. Our data suggest that emm87 is involved in pathogenesis by modulating the interaction between S. pyogenes and innate immune cells.
Insights
The M87 protein of Streptococcus pyogenes enhances bacterial survival against immune cells and promotes severe infections. Deleting this emm87 gene reduced mortality in a mouse model, highlighting its role in pathogenesis.
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Streptococcus pyogenes is a major human pathogen identified by its emm gene, which encodes the M protein.
- The M/emm87 strain's prevalence is increasing in invasive infections, but the role of its M87 protein in virulence is unknown.
Purpose of the Study:
- To investigate the role of the M87 protein in Streptococcus pyogenes pathogenesis.
- To determine how the M87 protein interacts with the host immune system.
Main Methods:
- Targeted mutagenesis to create emm87 deletion mutants.
- Assays for bacterial resistance to neutrophil and whole blood killing.
- Measurement of IL-1β release from macrophages.
- Assessment of epithelial cell adherence and nasal colonization.
- Evaluation of bacterial loads and mortality in a murine systemic infection model.
Main Results:
- The M87 protein enhances resistance to immune cell killing and promotes IL-1β release.
- Deletion of emm87 did not affect bacterial adherence or colonization.
- Loss of emm87 significantly reduced mortality and bacterial burden in a mouse model of systemic infection.
Conclusions:
- The M87 protein is a virulence factor for Streptococcus pyogenes.
- emm87 contributes to pathogenesis by modulating interactions with innate immune cells, impacting bacterial survival and host response.
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