# Quorum Sensing Regulation of Competence and Bacteriocins in _Streptococcus pneumoniae_ and _mutans_
## 10 Additional Inputs Regulating Competence in _S. mutans_
would help to discourage the inclination to name a gene based on homology and preliminary phenotypes alone [4]. The resulting surplus of names for an individual gene in _S. mutans_ has created confusion, unnecessarily biasing how researchers new to the field approach their QS pathway of interest. For example, the gene product encoded in locus SMU.1914c, predicted to belong to the type II family of bacterioxins, has been referred to in the literature as competence-induced peptide B (CipB) [22], Mutacin V [23], bacteriocin _Streptococcus mutans_ A (BsmA) [24], and non-lantibiotic mutacin C (NlmC) [23]. Maintaining a consistent nomenclature, as well as including specific loci identifiers (i.e., strain specific loci IDs) when reporting gene names, might alleviate some of this confusion (see Table 1). Understanding the regulation of competence pathways has empowered researchers to genetically manipulate, under laboratory conditions, various species of _Streptococcus_ including _S. mutans_, _S. thermophilus_, and _S. pneumoniae_[7; 31; 60]. This advance has greatly benefited the study of these organisms in contexts other than competence, by facilitating relatively rapid gene deletions and/or modifications. As many important pathogenic _Streptococcus_ species encode putative competence pathways, yet are currently non-transformable under laboratory conditions, elucidating the conditions to promote natural transformation in these organisms could greatly enhance their rate of genetic investigation. Recently, _comR_ genes of the Type-II ComRS QS pathways (conserved amongst the mutans, bovis, and pyogenic streptococcal groups) were expressed in an _S. mutans_ background to demonstrate that these ComR variants elicited SigX activity upon stimulation with XIP. The synthetic peptides added corresponded to a predicted mature XIP encoded near the C-terminus of each genome's putative _comS_. In this way, productive ComR/XIP activity was confirmed in _S. pyogenes_, and _S. suis_[66; 89; 91]. Interestingly, previously unstudied ComRs encoded in _Streptococcus agalaciae_, _Streptococcus dysgalaiciae_, and two Bovis group isolates exhibited SigX reporter activity in a dose-responsive manner when stimulated with the predicted cognate XIP. These results suggest that ComRS may function to regulate SigX within these organisms' respective genome [66]. While these preliminary results may seem promising, it is possible that unknown regulatory mechanisms are in place, similar to what is predicted in _S. pyogenes_, impeding the demonstration of natural transformation in these species [89]. To further the understanding of what is required for the development of competence in _Streptococcus_, an extensive report by [PERSON] et al. [94] proposed a defined core gene set required for natural transformation in _S. mutans_. In this study, six new tiling microarray data sets were analyzed, compared, and reconciled with five previously published transcriptome profiles. The authors improved upon the past microarray experiments by using a high density tiling array, by controlling for potential antisense artifacts, and by preparing samples from early log-phase cultures to minimize potential metabolic effects on signaling [94]. As a result of their meticulous methodology, [PERSON] et al. were able to define the BlpH, ComR, and SigX regulons as discrete sets of transcripts [94]. Additionally, this study confirmed previous findings that ComE is directly regulated by SigX [25; 83]. Finally, and most importantly, the authors aligned the predicted SigX regulon of five additional _Streptococcus_ species (_S. pneumoniae_, _Streptococcus gallolyticus_, _Streptococcus sanguinus_, _S. pyogenes_, and _S. thermophilus_) to that of _S. mutans_ to clearly compare gene expression levels between species. This broad comparison allowed for the identification of a pan-streptococcal core gene set regulated by SigX, potentially facilitating the identification of species-specific regulatory pathways governing the transition to the competent state [94].