A teichoic acid-like wall modification associated with immune suppression is socially regulated in <i>Streptococcus pyogenes</i>

<i>Streptococcus pyogenes</i> (group A streptococcus [GAS]) is a human-restricted pathogen with a range of clinical manifestations and worldwide prevalence. The GAS Rgg2/Rgg3 quorum-sensing (QS) system, a cell-to-cell communication network, modifies the cell surface, resulting in increased lysozyme resistance, biofilm formation, and expression of the <i>qim</i> operon which is responsible for modulation of innate immune responses in macrophages. The operon encodes 10 genes with predicted homology to enzymes involved in bacterial cell surface-associated carbohydrate and teichoic acid biosynthesis pathways. Comparing extracts of GAS cell wall polysaccharides between wild type and operon mutants showed that QS-induced genes modify the <i>S. pyogenes</i> cell surface by adding a wall teichoic acid-like <i>N</i>-acetylglucosamine-linked ribitol (GlcNAc-Rbo) moiety. A fluorescently labeled phage receptor-binding protein, RBP-13-GFP, that recognizes GlcNAc-decorated ribitol phosphate repeats, bound to the GAS surface only when <i>qim</i> expression was induced. Deletion of the <i>qim</i> operon eliminated RBP-13-GFP binding, diminished bacterial colonization, and significantly attenuated GAS pathogenesis in a murine skin infection model. These findings indicate that GAS has evolved a strategy to evade innate immune response by presenting a previously unknown carbohydrate moiety upon QS.IMPORTANCE<i>Streptococcus pyogenes</i> is a major human pathogen, responsible for diverse clinical manifestations of both superficial and invasive infections, and can lead to post-infection sequelae like rheumatic heart disease, whose prevalence on a global scale rivals that of the most serious pathogens. Invasive <i>S. pyogenes</i> infections are currently on the rise worldwide, notably correlating with increasing pediatric cases of scarlet fever and enhancing the concern for long-term complications. There is much that remains unknown about <i>S. pyogenes</i> virulence and pathogenicity, and studies focused on understanding basic systems regulating virulence factors could lead to better therapeutics and translational research. We show here one such example, where a bacterial communication system regulating a virulence mechanism relevant to <i>in vivo</i> infection confers the ability to alter the host's innate immune response. We find that modifications to the cell wall arise when this virulence system is activated, which has a direct role in host-pathogen interactions. Further research into this system could provide a mechanism for disruption and serve to treat <i>S. pyogenes</i> infection.