Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A.

Streptococcus pyogenes nuclease A (SpnA) interacts with complement membrane attack complex components to inhibit MAC assembly, revealing a novel immune evasion mechanism.

• Why it matters: Understanding how bacteria subvert host immunity is crucial for developing new treatments, as the molecular details of these interactions are often unclear, limiting therapeutic options.
• What they did: The study used hydrogen-deuterium exchange mass spectrometry, cryo-EM, affinity-pulldown, cross-linking mass spectrometry, and integrative modeling to analyze SpnA structure and its interaction with C5b67, identifying conserved binding interfaces.
• The result: Findings suggest SpnA prevents functional MAC assembly through conserved interactions, uncovering a new target for potential therapies against S. pyogenes infections.