Streptococcus suis adenosine synthase functions as an effector in evasion of PMN-mediated innate immunit

Area of Science:

• Microbiology
• Immunology
• Infectious Diseases

Background:

• Streptococcus suis serotype 2 (S. suis 2) is a significant pathogen causing sepsis and meningitis in pigs and humans.
• Understanding S. suis 2's survival mechanisms in human blood is crucial for developing effective therapies.
• Evasion of polymorphonuclear leukocyte (PMN)-mediated innate immunity is a key factor in S. suis 2 pathogenesis.

Purpose of the Study:

• To identify novel virulence factors enabling S. suis 2 to evade innate immunity.
• To investigate the role of adenosine synthesis in S. suis 2 survival within human blood.
• To elucidate the mechanism by which S. suis 2 inhibits PMN function.

Main Methods:

• Bioinformatics analysis to identify potential virulence factors.
• Biochemical assays to determine enzyme activity (5′-nucleotidase).
• In vitro experiments using human blood to assess PMN function (oxidative activity, degranulation) and S. suis 2 survival.
• In vivo piglet infection model to evaluate bacterial virulence.

Main Results:

• A cell wall-anchored protein, designated Ssads (adenosine synthase), was identified in S. suis 2.
• Ssads converts adenosine monophosphate (AMP) to adenosine, facilitating bacterial escape from phagocytic clearance.
• Ssads inhibits PMN defense mechanisms, including oxidative activity and degranulation, via A₂a receptors.
• An Ssads-deficient mutant exhibited reduced virulence in a piglet infection model.

Conclusions:

• Ssads is a novel virulence factor of S. suis 2 that promotes immune evasion.
• Adenosine synthesis by Ssads is critical for S. suis 2 survival in human blood by inhibiting PMN activity.
• Targeting Ssads or the adenosine pathway may represent a therapeutic strategy against S. suis 2 infections.