Streptococcus suis AdcA interacts with factor H and inhibits C3b deposition on the bacteria to participate in...

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Streptococcus suis is a significant zoonotic pathogen.
• Pathogens employ strategies to evade host immune responses, such as complement attack.
• Complement component C3b plays a crucial role in opsonophagocytosis and pathogen clearance.

Purpose of the Study:

• To identify proteins on Streptococcus suis that interact with complement component C3b.
• To elucidate the mechanism by which S. suis evades complement-mediated killing.
• To investigate the role of the identified protein, AdcA, in S. suis pathogenicity.

Main Methods:

• Co-immunoprecipitation (Co-IP) and Western blotting to identify protein interactions.
• Far-western blot analysis to confirm direct protein interactions.
• Construction of gene deletion and point mutants (ΔadcA, ΔadcA_FH(P-G), ΔadcA_FH(Y-P)).
• Molecular docking to predict interaction sites between AdcA and Factor H (FH).
• Assessment of C3b deposition, opsonophagocytosis, serum survival, and bacterial loads in mice.

Main Results:

• AdcA, a Zn²⁺ transporter and cell wall protein of S. suis, was identified to interact with complement regulatory factor H (FH), not directly with C3b.
• Deletion of adcA led to increased C3b deposition on the bacterial surface.
• Mutants lacking AdcA or its FH interaction sites showed reduced resistance to opsonophagocytosis and lower serum survival rates.
• Deletion of adcA significantly decreased bacterial loads in mouse tissues.

Conclusions:

• AdcA facilitates complement evasion by binding to FH, thereby inhibiting C3b deposition on S. suis.
• This interaction with FH protects S. suis from complement-mediated clearance and enhances its survival and pathogenicity.
• AdcA contributes to S. suis virulence through both complement evasion and its known role in zinc transport.