# Quorum Sensing Regulation of Competence and Bacteriocins in _Streptococcus pneumoniae_ and _mutans_
## 3 The Competence Pathway in _Streptococcus pneumoniae_  
The study of natural transformation in bacteria began after [PERSON] observed the transfer of morphological traits between different strains of _S. pneumoniae_. This transfer of phenotypes was later shown to be the result of DNA exchange regulated by a secreted peptide pheromone, the competence-stimulating peptide (CSP) [7]. The precursor peptide of CSP, ComC, contains an N-terminal leader peptide that shares homology with leader peptides found in the class II family of unmodified bactericidal peptides [8; 9]. This leader sequence also contains a double-glycine motif that directs the pre-peptide for export and processing through an ABC transporter/protease, ComAB [7; 9; 10]. During export, ComC is cleaved by ComAB immediately after the double-glycine motif to yield the active CSP [10]. No other modifications to CSP are known to occur in _S. pneumoniae_, thereby distinguishing CSP from the analog mutacin-inducing peptide (MIP) (see Table 1) in _S. mutans_, which is further processed extracellularly by the protease SepM [11]. Extracellular CSP then binds and activates the cognate histidine kinase receptor ComD of the ComCDE two-component signal-transduction pathway (TCST). Activation of ComD results in autophosphorylation and the subsequent transfer of a phosphoryl group (-P) to the cytosolic response regulator ComE [12; 13; 14]. Phosphorylated ComE (ComE-P) binds to a conserved promoter sequence, referred to as a ComE-binding site, or Ceb, found upstream of the alternative sigma factor gene \(sigX/comX\), for which there are two identical genomic copies within the _S. pneumoniae_ genome [14; 15; 16]. \(comX\) activity is essential for the expression of many genes required for competence (for recent reviews see [4; 17; 18]) [14; 15; 19; 20]. This conserved Ceb element is also found near the \(comAB\) operon as well as the \(comCDE\) operon. ComE-P binds at the Ceb in the promoter region (P\({}_{\text{Ceb}}\)) of these operons, among others, to activate gene expression, resulting in the amplification of the core components of the CSP signal transduction pathway [20; 21] (Figure 1). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**S. mutans Locus ID** & **Gene Product Name(s)** & **Function** & **References** \\ \hline SML\(\_\)1914c & Cipb, Mutaci V, NimC, B BmA & Type II bacteriocin & [22; 23; 24] \\ SMU\(\_\)1915 & Mipr,Com/CSP & Type I Nucleotide/pheromone & [25; 26] \\ SMU\(\_\)286 & Nimr,ComA & Bacteri transporter & [11; 27; 28] \\ SMU\(\_\)287 & Nimr,ComB & Nimr accessory factor & [11; 27; 28] \\ SMU\(\_\)1916 & BpH,Comb & Histidine kinase & [26; 29] \\ SMU\(\_\)1917 & Bipr,ComE & Response regulator & [26; 29] \\ SMU\(\_\)1997 & Sigr,ComE & Alternative sigma factor & [30; 31] \\ SMU\(\_\)61 & ComR & Type-II ComR; Transcriptional regulator of competence & [31] \\ N/A & ComS & Pre-peptide of XIP pheromone & [31] \\ SMU\(\_\)1997-1898 & CAl,ComA & ABC transporter ATP-binding protein/permease & [30; 32] \\ SMU\(\_\)1900 & CAlB,ComB & ABC transporter accessory protein & [30; 32] \\ SMU\(\_\)381c & Smu,81c & Type-IComR; Putative transcriptional regulator & [31] \\ \hline \hline \end{tabular} Gene names in bold are the designations used in this review and are based on the current understanding of the gene product’s function in _S. mutans_. The species-specific locus IDs are included for further clarification. Alternative names proposed for each gene are listed following the designated names. References cited correspond to the original report(s) referencing each locus with either the designated or alternative name(s).  
\end{table} 
Table 1: Nomenclature of selected genes from the _Streptococcus mutans_ UA159 bacteriocin and competence quorum sensing pathways. Figure 1: The ComABCDE quorum sensing (QS) pathway of _Streptococcus pneumoniae_. The two phases of competence development are controlled by ComE, for induction of early genes, and by ComX, for induction of late genes.