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==Introduction==

The expression of the chromosomal ''spa'' gene, which encodes the protein A, is regulated by the ''agr'' system and Rot. The level of expression is up-regulated by Rot and down-regulated by ''agr''.  

Furthermore protein A serves as a virulence factor to ''Staphylococcus aureus'' . It is essential for the colonization and infections mediated by this kind of bacteria<ref>Bronner, S., Monteil, H., & Prévost, G. (2004). Regulation of virulence determinants in Staphylococcus aureus: complexity and applications. FEMS microbiology reviews, 28(2), 183-200</ref>.

The structural details of protein A were solved by the nuclear magnetic resonance method. The length of the amino acid chain of protein A contains 508 residues. The amino acids cystein and tryptophan do not occur in the amino acid sequence. The molecular weight of the described protein is 55439 Dalton and it consists of only one protein chain.  

The 3D structure<ref>PDB ID: 1SS1; S.Sato, T.L.Religa, V.Daggett, A.R. Fersht (2004) Testing protein-folding simulations by experiment: B domain of protein A. Proc.Natl.Acad.Sci.USA 101: 6952-6956</ref> is build up of three α-helixes and it consists of five extracellular domains, which are designated as E, D, A, B and C. Furthermore the protein contains cell-wall spanning regions, called X_r and X_c, and a hydrophobic membrane spanning domain, which is distal to LPXTG and consists of 18-20 residues<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. (2000). Protein A is the von Willebrand factor binding protein on Staphylococcus aureus, 2149-2156</ref>. Protein A exists in a secreted and a cell wall anchored form. If it is bound to the cell wall of ''Staphylococcus aureus'' it is covalently linked to the peptidoglycan via its C-terminal domain.  

[[Image:Spa-1.jpg]]

Moreover, invasive ''Staphylococcus aureus disease'' are often associated with the complication of endovascular infections. In order to cause this kind of complication staphylococci must first adhere to endovascular foci and colonize these tissues. One of the factors released by endothelial cells and by platelets is the von Willbrrand factor (vWF). This factor mediates the adhesion of platelets at damaged endothelial sites. It was shown that vWF binds to and also promotes the adhesion of staphylococcal cells to vWF-absorbed surfaces. It could also be demonstrated that the recognition of vWF is mediated by the staphylococcal protein A.  

Protein A defective mutants have shown reduced virulence in murine models. These observations can be explained most likely by the antiphagocytic effect of protein A binding IgG Fc fragments<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. (2000). Protein A is the von Willebrand factor binding protein on Staphylococcus aureus, 2149-2156</ref>.

In a normal case of phagocytosis, the bacterium is eliminated during intracellular digestion, thanks to hydrolytic enzymes of phagocyte. At first, the particle is recognized and sticks on the phagocyte. The recognition is possible thanks to phagocyte membrane receptors, which recognize the Fc domain of immunoglobulins. Then the bacteria enter into the phagocyte by a process of endocytosis. The intracellular digestion takes place, and the bacterium is degraded by enzymes. To finish, cell fragments are removed by exocytosis.  

In the case of S.aureus, in the serum, the interaction between Fc domain and protein A leads to the attachment in a wrong direction of the IgG to the bacterium: then, the recognition is not allowed and the cascade of reactions necessary for phagocytosis does not occur. By stopping this process and through other virulence factors, bacterial colonization is allowed, through the growth and dissemination of bacteria into the organism<ref>http://en.wikipedia.org/wiki/Protein_A?oldid=252478781</ref>.