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=== Biofilm formation === [[Biofilm]]s 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]].<ref name="pmid21829369">{{cite journal | vauthors = Chang JC, LaSarre B, Jimenez JC, Aggarwal C, Federle MJ | title = Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development | journal = PLOS Pathogens | volume = 7 | issue = 8 | pages = e1002190 | date = August 2011 | pmid = 21829369 | pmc = 3150281 | doi = 10.1371/journal.ppat.1002190 | doi-access = free }}</ref> 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.<ref name="pmid21829369"/> 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.<ref name="pmid21829369"/> 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.<ref name="pmid21829369"/>
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