# Quorum Sensing Regulation of Competence and Bacteriocins in _Streptococcus pneumoniae_ and _mutans_
## 3 The Competence Pathway in _Streptococcus pneumoniae_
Early genes required for competence include _comE_, _comAB_, _comCDE_, _comXI_/_comX2_, and _comW_. Dispensable early genes include _comM_ as well as _blpABC_, and _blpXYZ_[20]. Phosphorylated ComE binds at P\({}_{\text{Ceb}}\), a promoter site containing a ComE binding site (Cbe) [14; 16; 21]. [PERSON] et al. [33] recently demonstrated dual regulation of the _blpABC_ operon either by ComE or BlpR in _S. pneumoniae_ (denoted by P\({}_{\text{Ceb}}\)/P\({}_{\text{BlpR-box}}\)) [10]. The alignment of the upstream sequence of ComE- and BlpR-regulated genes are shown in the figure inset. The consensus sequences for P\({}_{\text{Ceb}}\)- and P\({}_{\text{BlpR-box}}\)-direct-repeat binding motifs in the _S. pneumoniae_ TIGR4 genome are compared with the upstream sequences of _qsrA_ (locus ID: SP_1717), _blpX_ (locus ID: SP_0544) and the direct-repeat hybrid motif (P\({}_{\text{Ceb}}\)/BlpR-box) located upstream of _blpA_ (locus ID: SP_0530). Highlighted in orange is the guanine base pair that is conserved in ComE-regulated promoters, permitting ComE to regulate expression of the _blpABC_[33]. Highlighted in green are base pairs conserved in the proximal motif of BlpR-regulated promoters. This sequence alignment has been adapted from [PERSON] et al. [33]. The late genes are directly regulated by the ComX/RNAP (RNA polymerase) complex and consist of genes required for DNA uptake, homologous recombination as well as the lytic genes, _cibABC_, _cbpD_, and _lytA_, encoding effectors of fratricide [20]. The ComAB complex exports and processes ComC into the mature peptide pheromone CSP [10]. Recently, ComAB was demonstrated to export and process BlpC. This connection between the bacteriocin and competence QS system pathways clarifies how BlpC activity is detected in strains lacking a functional BlpC exporter (BlpA) [33; 34]. The induction of competence in _S. pneumoniae_ is divided into two temporally distinct phases, the early and the late, regulated by ComE-P or ComX, respectively [19; 20]. Besides activating transcription of _comX_, _comAB_, and _comCDE_, ComE-P also activates transcription of at least 17 other genes, several of which are required for the development of the competent state [20]. The early gene (defined by the maximal expression between 7.5 and 10 min post-CSP treatment), _comW_, is important in natural transformation as it is required for stabilizing SigX protein levels and enabling SigX activity by way of an unknown mechanism [20; 35; 36; 37]. Early genes observed to contribute to transformation, yet are dispensable, include _comM_, a membrane protein that imparts cellular immunity towards lytic enzymes as well as _blpAB_ which encodes a bacteriocin transporter that shares homology with the CSP exporter, _comAB_[38; 39; 40] (Figure 1). The expression levels of ComX-induced late genes peak approximately 12.5 to 15 min post-CSP induction [20]. Although the late genes comprise over 80 genes, only 14 have been identified as essential for transformation [20]. These required genes include those encoding the DNA-uptake machinery and the recombination machinery (also, referred to as the transformasome (see [PERSON] et al. [41] for a review) (Figure 1).