Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial...

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Staphylococcus aureus is a major human pathogen causing diverse infections.
• S. aureus evades the host immune system by interacting with complement regulators.
• Previous work showed S. aureus binds C4b-binding protein (C4BP), inhibiting complement-mediated opsonization.

Purpose of the Study:

• To identify the S. aureus surface protein responsible for C4BP binding.
• To investigate the functional consequences of SdrE-C4BP interaction on complement activation and bacterial clearance.

Main Methods:

• Recombinant SdrE and Bbp (an SdrE allelic variant) were used to assess C4BP and Factor H binding in serum.
• Gain-of-function studies were performed using Lactococcus lactis expressing SdrE or Bbp.
• Classical pathway-mediated opsonization and bacterial killing by neutrophils were quantified.

Main Results:

• S. aureus surface protein SdrE and its variant Bbp directly bind C4BP and Factor H in human serum.
• Lactococcus lactis expressing SdrE or Bbp showed a two-fold increase in C4BP and Factor H binding.
• Expression of SdrE or Bbp reduced classical complement pathway opsonization and bacterial killing by half.

Conclusions:

• SdrE and Bbp are identified as S. aureus surface proteins that bind C4BP.
• This interaction inhibits classical complement pathway-mediated opsonization.
• The binding of SdrE/Bbp to C4BP contributes to S. aureus immune evasion and pathogenesis.