William Powell

Introduction: Staphylococcus aureus is a common commensal bacterium but can become pathogenic and results in over 1 million skin and soft tissue infections alone in the U.S as well as endocarditis, sepsis, musculoskeletal infections, and toxic shock syndrome^1-2. S. aureus uses a variety of virulence factors and defense mechanism to avoid the innate immune system with Staphylococcal Compliment Inhibitor (SCIN) being a primary one³. SCIN functions by inhibiting the function of C3 convertase and stops deposition of C3b on the bacterial surface to prevent phagocytosis, opsonization, cell lysis, and inflammation³. SCIN also plays an important role in early biofilm formation which protects the bacteria from chemical and physical insults providing a safe place for the bacteria to replicate⁴. Methods: Levels of SCIN expression were measured using a SCIN promoter-GFP construct during biofilm formation with immunofluorescence⁴. Anti-SCIN antibodies were used to determine the amount of SCIN present by measuring the amount of unbound SCIN IgG⁴. ELISA was used to measure C5a release when SCIN and human serum were present. Flow cytometry measured the amount of C3b deposition and rabbit erythrocyte lysis when SCIN was inhibited⁵. Finally, a radiolabeled monoclonal antibody was designed to define deposition patterns of SCIN on the surface of the bacteria⁵. Results: SCIN binds to the surface of the bacteria where the C3 convertase is located and inhibits the deposition of C3b⁵. Inhibition of SCIN with a monoclonal antibody results in increased deposition of C3b on the cell surface indicting SCIN’s importance in inhibiting the complement system⁵. SCIN plays a role in biofilm formation as decreasing levels anti-SCIN antibodies are detected over 24 hours of biofilm growth⁴. Finally, a human monoclonal antibody against SCIN is effective at diagnosing S. aureus infections.^5,6 Conclusions: Studies indicated that SCIN is a potent antigen in innate immune evasion that allows for increased bacterial growth and virulence. It was shown that the use of anti-SCIN antibodies could be used to discriminate between various S. aureus MSK infections and other causative agents⁶. Finally, it was shown that while an anti-SCIN monoclonal antibody is not a likely candidate for use in a vaccine since not all strains are SCIN positive, anti-SCIN monoclonal antibodies could potentially be useful in diagnosis of S. aureus in a clinical setting⁵.

1. Dayan GH, Mohamed N, Scully IL, et al. Staphylococcus aureus: the current state of disease, pathophysiology and strategies for prevention. Expert Rev Vaccines. 2016;15(11):1373-1392. doi:10.1080/14760584.2016.1179583
2. Thomer L, Schneewind O, Missiakas D. Pathogenesis of Staphylococcus aureus Bloodstream Infections. Annu Rev Pathol. 2016;11:343-364. doi:10.1146/annurev-pathol-012615-044351
3. Nasser A, Moradi M, Jazireian P, et al. Staphylococcus aureus versus neutrophil: Scrutiny of ancient combat. Microb Pathog. 2019;131:259-269. doi:10.1016/j.micpath.2019.04.026
4. Sultan AR, Swierstra JW, Lemmens-den Toom NA, et al. Production of Staphylococcal Complement Inhibitor (SCIN) and Other Immune Modulators during the Early Stages of Staphylococcus aureus Biofilm Formation in a Mammalian Cell Culture Medium. Infect Immun. 2018;86(8):e00352-18. Published 2018 Jul 23. doi:10.1128/IAI.00352-18s
5. Hoekstra H, Romero Pastrana F, Bonarius HPJ, et al. A human monoclonal antibody that specifically binds and inhibits the staphylococcal complement inhibitor protein SCIN. Virulence. 2018;9(1):70-82. doi:10.1080/21505594.2017.1294297
6. Muthukrishnan G, Soin S, Beck CA, et al. A Bioinformatic Approach to Utilize a Patient’s Antibody-Secreting Cells against Staphylococcus aureusto Detect Challenging Musculoskeletal Infections. Immunohorizons. 2020;4(6):339-351. Published 2020 Jun 22. doi:10.4049/immunohorizons.2000024