Molecular and Genetic Determinants Governing Cell Killing and Competence in Streptococcus Mutans

Streptococcus mutans, the primary etiological agent of dental caries, has evolved complex quorum sensing (QS) systems that regulate the production of bacteriocins and the entry into the competent state, a requirement for natural transformation. Natural transformation provides bacteria with a mechanism to repair damaged genes or as a source of new advantageous traits. Bacteriocins are secreted antimicrobial peptides that induce lysis upon interaction with target membranes and are important for providing a source of DNA. The first chapter of this review compares the QS pathways regulating transformation and bacteriocin production in S. mutans with those of Streptococcus pneumoniae, a common human pathogen. The second chapter focuses on the ComRS QS pathway in S. mutans, which regulates natural transformation. The conservation patterns of this ComRS locus across the Mutans, Pyogenic and Bovis groups of Streptococcus facilitated the discovery of a WW-motif encoded in the C-terminal end of putative XIP peptides derived from these groups. We developed a test-bed reporter strain that allowed for expression of ComRs derived from species of these groups to test for activity with the putative ligand XIP. Additionally, we present the crystal structure of the Streptococcus suis ComR and use mutational analysis to confirm structural domains and to identify important residues in ComR/XIP activity. In the last section of this thesis, I probe the connection between the QS pathway regulating bacteriocin production (the BlpRH system) and the pathway controlling the induction of competence (the ComRS system) with an emphasis on the activity of a putative bacteriocin, CipB.