Srr2, a multifaceted adhesin expressed by ST-17 hypervirulent Group B Streptococcus involved in binding to both...

Area of Science:

• Microbiology
• Molecular Biology
• Infectious Diseases

Background:

• Group B Streptococcus (GBS) ST-17 clone is a major cause of neonatal meningitis.
• Serine-rich repeat glycoproteins (Srr) are cell wall-anchored proteins in GBS, with Srr2 specific to ST-17 strains and Srr1 found in non-ST-17 strains.

Purpose of the Study:

• To investigate the binding capacity of GBS Srr proteins (Srr1 and Srr2) to host fibrinolysis pathway components.
• To elucidate the role of Srr2 in GBS pathogenesis, particularly in neonatal meningitis.

Main Methods:

• Comparative genome analysis of GBS strains.
• In vitro binding assays to assess Srr protein interactions with plasminogen, plasmin, and fibrinogen.
• Murine model of meningitis to evaluate bacterial survival and persistence.

Main Results:

• Srr2 specifically binds plasminogen and plasmin, while Srr1 does not.
• ST-17 strains exhibit enhanced fibrinogen binding due to higher Srr2 surface display and affinity.
• Srr2-mediated binding leads to bacterial aggregation and increased phagocytosis, with Srr2 enhancing bacterial survival against phagocytic killing.
• Srr2 promotes bacterial persistence in a murine meningitis model.

Conclusions:

• Srr2 acts as a multifaceted adhesin, enabling the GBS ST-17 clone to exploit host coagulation factors.
• This interaction facilitates bacterial dissemination and invasiveness, contributing to the development of neonatal meningitis.
• Targeting Srr2 may offer a therapeutic strategy against GBS ST-17 infections.