Staphylococcus aureus Protein A (SpA)

Staphylococcus aureus Protein A (SpA) is a 42 kDa surface protein and a critical virulence factor that enables S. aureus to evade the host immune system. It consists of five conserved immunoglobulin-binding domains (E, D, A, B, and C) that bind with high affinity to the Fc region of IgG, effectively coating the bacterium in host antibodies in an orientation that prevents recognition by phagocytic cells (UniProtKB - P02976). Furthermore, SpA functions as a B-cell superantigen by binding to the Fab region of VH3-family B-cell receptors, leading to polyclonal B-cell expansion and subsequent exhaustion or apoptosis, which prevents the development of a protective adaptive immune response (Kim et al., 2010, J Exp Med). Given its multifaceted role in pathogenesis, SpA is a major target for therapeutic monoclonal antibodies and vaccine candidates designed to neutralize its activity and enhance bacterial clearance (Varshney et al., 2018, JCI Insight). For instance, the monoclonal antibody 514G3 has been developed to target SpA to treat S. aureus bacteremia by facilitating opsonophagocytosis. In addition to its clinical relevance, the high affinity of SpA for the Fc region is extensively exploited in biotechnology for the industrial purification of monoclonal antibodies.

Other names

Protein AStaphylococcal protein Aspa gene productImmunoglobulin-binding protein A

Neutralization of Protein A to prevent its binding to the Fc region of host IgG and the VH3-type B-cell receptor, thereby restoring opsonophagocytosis and preventing B-cell apoptosis.