image of
Streptococcus pyogenes (orange) during
phagocytosis with a human
neutrophil (blue)
Serotyping In 1928,
Rebecca Lancefield published a method for serotyping
S. pyogenes based on its cell-wall polysaccharide, a
virulence factor displayed on its surface. Care should be taken when using lancefield antigen typing to identify
S. pyogenes as
Streptococcus dysgalactiae and the
Streptococcus anginosus group can possess group A antigen as well. Later, in 1946, Lancefield described the serologic classification of
S. pyogenes isolates based on components of their surface
pili (known as the T-antigen) which are used by bacteria to attach to host cells. As of 2016, a total of 120
M proteins have been identified. These M proteins are encoded by 234 type
emm genes with greater than 1,200 alleles. Some of the phages may be defective, but in some cases active phage may compensate for defects in others. In general, the genome of
S. pyogenes strains isolated during disease are >90% identical, they differ by the phage they carry.
Virulence factors S. pyogenes has several
virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers. A carbohydrate-based
bacterial capsule composed of
hyaluronic acid surrounds the bacterium, protecting it from
phagocytosis by
neutrophils. M protein also inhibits
opsonization by the alternative
complement pathway by binding to host complement regulators. The M protein found on some serotypes is also able to prevent opsonization by binding to
fibrinogen.
Genome The genomes of different strains were sequenced (genome size is 1.8–1.9 Mbp), encoding about 1700-1900 proteins (1700 in strain NZ131, 1865 in strain MGAS5005). Complete genome sequences of the type strain of
S. pyogenes (NCTC 8198T = CCUG 4207T) are available in
DNA Data Bank of Japan,
European Nucleotide Archive, and
GenBank under the accession numbers LN831034 and CP028841.
Biofilm formation Biofilms are a way for
S. pyogenes, as well as other bacterial cells, to communicate with each other. In the biofilm gene expression for multiple purposes (such as defending against the host immune system) is controlled via
quorum sensing. One of the biofilm forming pathways in GAS is the Rgg2/3 pathway. It regulates SHP's (short hydrophobic peptides) that are quorum sensing pheromones, a.k.a. autoinducers. The SHP's are translated to an immature form of the pheromone and must undergo processing, first by a metalloprotease enzyme inside the cell and then in the extracellular space, to reach their mature active form. The mode of transportation out of the cell and the extracellular processing factor(s) are still unknown. The mature SHP pheromone can then be taken into nearby cells and the cell it originated from via a transmembrane protein, oligopeptide permease. In the cytosol the pheromones have two functions in the Rgg2/3 pathway. Firstly, they inhibit the activity of Rgg3 which is a transcriptional regulator repressing SHP production. Secondly, they bind another transcriptional regulator, Rgg2, that increases the production of SHP's, having an antagonistic effect to Rgg3. SHP's activating their own transcriptional activator creates a positive feedback loop, which is common for the production for quorum sensing peptides. It enables the rapid production of the pheromones in large quantities. The production of SHP's increases biofilm biogenesis. It has been suggested that GAS switches between biofilm formation and degradation by utilizing pathways with opposing effects. Whilst Rgg2/3 pathway increases biofilm, the
RopB pathway disrupts it. RopB is another Rgg-like protein (Rgg1) that directly activates SpeB (streptococcal pyrogenic exotoxin B), a cysteine protease that acts as a virulence factor. In the absence of this pathway, biofilm formation is enhanced, possibly due to the lack of the protease degrading pheromones or other Rgg2/3 pathway counteracting effects. == Pathology ==