Figure 1.

Streptococcus pyogenes Rgg2 and Rgg3 quorum-sensing circuit. The regulatory circuit begins with production of small hydrophobic peptides (pre-SHP) that are exported and processed by the PptAB ABC-type transporter and Eep intramembrane protease, respectively. Extracellular SHPs may diffuse to other nearby cells (paracrine signaling) or be auto-stimulatory (autocrine signaling). SHPs are internalized by the oligopeptide importer Opp and subsequently interact with their receptors, the transcriptional regulators Rgg2 and Rgg3. When not bound to SHP, Rgg3 binds DNA and represses transcription of the shp gene promoters. However, Rgg3 releases DNA when engaged with SHP, derepressing gene transcription. Rgg2 works oppositely, acting as a transcriptional activator in response to bound SHP and causes an increase to SHP pheromone production. The endopeptidase PepO degrades SHP peptides and therefore can down-regulate the quorum-sensing pathway.