The Rgg 2/3 Quorum Sensing System Contributes to the Pathogenesis of Streptococcus pyogenes

This thesis seeks to characterize the physiological importance and molecular mechanism underlying a quorum system in Streptococcus pyogenes. This bacterium is most commonly found in the nasopharynx of its human host, where it can cause pharyngitis or persist asymptomatically for long periods of time. This thesis will focus on two elements of the Rgg2/3 quorum sensing system—its physiological relevance in the host and the mechanism of action of its uncharacterized target gene, spy49_0414c. We will present the results of our own experimentation with a colonization model, where we find that the Rgg2/3 system is required across multiple serotypes of GAS for colonization of the murine nasopharynx. Activation of the quorum sensing target genes occurs within one hour of inoculation into the murine nasopharynx. One of these genes, spy49_0414c, or stcA, is a primary target gene of the Rgg2/3 system that is activated almost 100-fold upon introduction into the mouse colonization model, and almost 1000-fold when the bacteria are exogenously stimulated with synthetic SHP. The gene is responsible for the production of a small, positively charged protein called StcA. The data in this thesis provides evidence that the StcA protein coats the surface of the QS-activated cells and alters the overall surface charge of the bacteria. This work provides novel insight into the physiological relevance of the Rgg2/3 quorum sensing system and highlights attractiveness as a potential drug target. The alteration of the bacterial cell surface by StcA begins to dissect one of the mechanisms in which the Rgg2/3 system may be functioning to alter the host-pathogen interaction. Continued investigation will identify additional factors involved in colonization of the host and will help lead to development of new drugs against the system.