M-proteine

Rebecca Lancefield identified the M protein of streptococci in 1928.

The M-protein is an important, cell-wall-standing, antiphagocytic virulence factor of the A-streptococcus. The molecule lies as an additional protein layer on the cell wall. The M protein is encoded by the M protein gene of the same name (emm). To date, 86 serovarieties are known.

The ability of S. pyogenes to persist in infected tissue is primarily due to the M protein. The M protein (esp.M1) confers on streptococci the ability to resist phagocytosis by polymorphonuclear leukocytes in the absence of type-specific antibodies (Anderson EL et al.2014). Thus, the importance of the M molecule is demonstrated in an M knockout mutant that has all the other surface and secretion molecules of the wild-type organism but cannot survive in human blood containing phagocytes (Perez-Casal J et al 1992).

Resistance to group A streptococcal infection is directly related to the presence of specific antibodies to the M molecule (Lancefield EC 1959; Lancefield RC 1962).

There is a high structural similarity between the M- protein and the human α-helical coiled-coil proteins. This leads to the assumption that the triggering of cross-reactive anti-M antibodies and T-cell receptors directed against these human proteins(antigenic mimicry) as a possible cause of S. pyogenes-associated autoimmune sequelae. These include acute rheumatic fever and/or poststreptococcal glomerulonephritis (usually M12). Typing of the M protein gene (emm typing) and its analysis has resulted in the development of a valid sequencing system for streptococci, allowing comparability between serovars.

Structure of the M protein: The M protein can be considered the archetypal molecule for those surface proteins that anchor to the Gram-positive bacterial cell wall via their C-terminal region. Since the M protein, as well as other surface proteins on streptococci, do not possess cytoplasmic domains, it is unlikely that binding of these molecules to specific ligands triggers a signal in the microbe to activate a gene product. It is much more likely that the binding triggers a conformational signal on the cell surface to carry out a specific function.

Streptococci normally infect the pharynx (and especially the tonsils) through contact with contaminated saliva. Upon entering the oral cavity, the organism first encounters the mucus lining the mucosal epithelium. Soluble components in the mucus, such as IgA, IgG, albumin, fibronectin, and others, can interact with their respective binding proteins on the streptococcal surface. This binding can trigger a series of conformational events on the surface of the bacterial particle that enable it to penetrate through the mucus to the epithelial surface. This must happen very quickly or the organism will be flushed into the gut and eliminated. Thus, the molecules necessary to initiate infection at all body sites are ready on the cell surface.

1. Anderson EL et al.(2014) The fibrinogen-binding M1 protein reduces pharyngeal cell adherence and colonization phenotypes of M1T1 group A Streptococcus. The Journal of Biological Chemistry. 289:3539–3546.
2. Lancefield RC (1928) The antigenic complex of Streptococcus hemolyticus. I Demonstration of a type-specific substance in extracts of Streptococcus hemolyticus. The Journal of Experimental Medicine 47:91-103.
3. Lancefield RC (1959) Persistence of type-specific antibodies in man following infection with group A streptococci. The Journal of Experimental Medicine 110:271-292.
4. Lancefield RC (1962) Current knowledge of the type-specific M antigens of group A streptococci. The Journal of Immunology 89:307-313.
5. Perez-Casal J et al.(1992) Introduction of the emm6 gene into an emm-deleted strain of Streptococcus pyogenes restores its ability to resist phagocytosis. Research in Microbiology 143:549-558.
6. Yamaguchi M et al (2013) Pleiotropic virulence factor - Streptococcus pyogenes fibronectin-binding proteins. Cellular Microbiology 15:503-511.