Protein a

Protein A is a protein of 40 to 60 kDa size that occurs as a virulence factor in the cell wall of Staphylococcus aureus. It is covalently bound to a peptidoglycan residue of the cell wall. Thus, protein A is detected in about 95% of all human pathogenic S. aureus strains. Protein A is very stable to high temperatures (> 100 °C) and denaturing agents. Protein A binds with high affinity many immunoglobulins (1 molecule of protein A binds at least 2 molecules of IgG) via its constant part (Fc, Fc receptor). Via this mechanism, S. aureus is hidden from phagocytes.

Due to its special properties to bind certain proteins (immunoglobulins), recombinant protein A is also used in biotechnology (Rigi G et al. 2019). Protein A binds mainly IgG via the constant part (Fc, Fc receptor) of the immunoglobulin by interaction with the heavy chain (Arbiser JL et al. 1995).

S. aureus uses this affinity to protect itself from immune system defenses. By binding to the Fc bond, immunoglobulins are bound to the cell wall the "wrong" way round (compared to their normal function). The bacterium is thus protected from opsonization and phagocytosis.

Protein A binds with high affinity to human IgG1 and IgG2 and to mouse IgG2a, IgG2b and IgG3. Human IgM, IgA and IgE are bound with moderate affinity. In contrast, protein A does not react with human IgG3 or IgD or with mouse IgM, IgA, or IgE. Mutants of S. aureus that cannot express protein A are phagocytosed more rapidly in vitro and show reduced virulence in infection models. Protein A is also able to kill B lymphocytes very efficiently.

1. Arbiser JL et al (1995) Leukocytoclastic vasculitis following staphylococcal protein A column immunoadsorption therapy. Two cases and a review of the literature. Arch Dermatol 131:707-709.
2. Rigi G et al (2019) A comprehensive review on staphylococcal protein A (SpA): Its production and applications. Biotechnol Appl Biochem 66:454-464.