Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Streptococcus pneumoniae is a common bacterium that can cause severe infections.
• The bacterium's surface interactions with host proteins are crucial for pathogenesis.
• Plasminogen (PLG) activation on the bacterial surface is a known virulence mechanism.

Purpose of the Study:

• To investigate the role of pneumococcal phosphoglycerate kinase (PGK) in binding and potentially utilizing host plasminogen (PLG).
• To elucidate the structural basis of the interaction between pneumococcal PGK and PLG.

Main Methods:

• Immune-electron microscopy to localize PGK on bacterial surfaces.
• Surface plasmon resonance (SPR) to analyze binding kinetics and affinity.
• Crystal structure determination of pneumococcal PGK.
• Peptide array analysis to map binding sites.
• Binding studies and enzymatic assays to confirm interactions with PLG and tissue plasminogen activator (tPA).

Main Results:

• PGK was found on the surface of both capsulated and non-capsulated S. pneumoniae strains, co-localizing with PLG.
• PGK specifically binds human and murine PLG with high affinity, particularly to kringle domains 1-4.
• The N-terminal region of PGK was identified as the PLG-binding site through structural and peptide array analyses.
• PGK was shown to interact with tissue plasminogen activator (tPA), facilitating plasmin formation and thrombus degradation.

Conclusions:

• Pneumococcal PGK acts as a surface receptor for host plasminogen.
• The structural insights into PGK-PLG interaction provide a basis for understanding its role in virulence.
• PGK's interaction with the fibrinolytic system (PLG and tPA) suggests a mechanism by which S. pneumoniae may evade host defenses or promote tissue damage.