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Updated: Oct 10, 2026
A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Characterization of a mouse-passaged, highly encapsulated variant of group A streptococcus in in vitro and in vivo
1Department of Clinical Microbiology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Abstract:
JRS4(HE), a highly encapsulated, mouse-passaged variant of group A streptococcal strain JRS4, was characterized. The mucoid phenotype of JRS4(HE) was preserved after extensive passage in vitro. The level and size of csrRS transcript in JRS4(HE) was similar to that of JRS4, yet JRS4(HE) expressed high levels of has and sagA and exhibited an increased activity of streptolysin S. These findings indicate that the CsrRS repressor system was inactive in JRS4(HE). JRS4(HE) adhered to HEp-2 cells at the stationary phase but did not internalize these cells. At midlogarithmic phase, JRS4(HE) neither adhered to nor internalized cells, because of an increased amount of hyaluronic acid. Mice injected subcutaneously with JRS4(HE) developed large, deep necrotic lesions. In contrast, mice challenged with JRS4 developed small, superficial lesions. Despite the use of a high inoculum, mice challenged with JRS4(HE) did not develop a lethal bacteremic infection. It is concluded that inactivation of CsrRS in vivo is insufficient to cause a spreading necrotic disease.
Insights
Inactivation of the CsrRS repressor system in group A Streptococcus JRS4(HE) led to increased virulence and necrotic lesions in mice. However, it was insufficient to cause a spreading bacteremic infection.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Group A Streptococcus (GAS) causes various infections, with virulence factors playing a key role.
- The CsrRS two-component system regulates GAS virulence gene expression.
- Understanding CsrRS regulation is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize JRS4(HE), a mouse-passaged variant of GAS strain JRS4 with a mucoid phenotype.
- To investigate the role of CsrRS inactivation in the virulence and pathogenesis of GAS.
Main Methods:
- Phenotypic characterization of JRS4(HE) including encapsulation and adherence assays.
- Analysis of csrRS, has, and sagA transcript levels and streptolysin S activity.
- In vivo studies using a mouse model to assess lesion development and bacteremia.
Main Results:
- JRS4(HE) maintained its mucoid phenotype and expressed high levels of has and sagA, indicating CsrRS inactivation.
- JRS4(HE) showed differential adherence to HEp-2 cells dependent on growth phase, attributed to hyaluronic acid.
- Subcutaneous JRS4(HE) injection caused deep necrotic lesions, but not lethal bacteremia, unlike the parental strain.
Conclusions:
- CsrRS inactivation in GAS leads to increased lesion severity.
- Hyaluronic acid production influences bacterial adherence.
- Inactivation of CsrRS alone is insufficient to induce a spreading necrotic disease in vivo.
