# Quorum Sensing Regulation of Competence and Bacteriocins in _Streptococcus pneumoniae_ and _mutans_
## 6 A Direct Link between _blp_ and _com_ Is Established in _S. pneumoniae_  
Recently, two groups independently uncovered direct links between the ComABCDP and the BlpABC/BlpRH pathways. As previously mentioned, \(\sim\)70%-80% of all sequenced pneumococcal isolates encode a non-functional BlpAB transporter [34; 52]. [PERSON] et al. [34] asked whether this degeneracy was correlated to gene loss within the BlpR-regulated BIR as a result of genetic drift. Interestingly, compared to genomes containing an intact _blpAB_ locus, there were no significant differences in the number of predicted bacteriocins encoded within the _blpAB_-deficient strains [24]. Experiments performed in a strain lacking a functional BlpAB transporter demonstrated natural induction of _blp_ loci during culture growth in a competence-permissive medium (C + Y, \(\geq\)7.4 pH) or upon exposure to sub-lethal concentrations of the antibiotics HPUra (6-(\(p\)-hydroxyphenylazo)-uracil), ciprofloxacin, and streptomycin. These induction profiles closely mimicked expression patterns previously associated with the ComE-regulated genes under identical conditions [55; 56; 57; 34].  
Similarly, [PERSON] et al. [33] demonstrated induction of _blp_ operons in response to exogenous CSP, even when the _comAB_ locus was knocked out. They also showed that this effect required intact _comE_, _blpC_, and _blpH_. Furthermore, this group observed decreased levels of secreted BlpC in the supernatants of strains lacking a ComAB transporter. As both BlpC and ComC pre-peptides encode an N-terminal leader peptide containing a double-glycine motif, this result suggested that perhaps the ComAB transporter was able to export and process BlpC as well as ComC [33]. Indeed, both [PERSON] et al. and [PERSON] et al. [34; 33] demonstrated that ComAB was responsible for the processing and exporting of pre-BlpC in a _blpA_ deficient mutant (Figure 1). However, the levels of matured BlpC detected in whole-cell lysates suggested that only \(\sim\)30% of the pre-BlpC peptide could be exported by ComAB when compared to a _comAB_/_blpA_ sufficient strain [33].  
The previous finding by [PERSON] et al., [40] that the hybrid direct-repeat motifs within the promoter region of the early genes _qsrAB_ could accommodate both ComE and BlpR, led [PERSON] et al. to probe this same possibility as an explanation for the CSP-induced expression of the _blpABC_ locus. When the distal motif of the _blpR_-box direct repeat upstream of _blpABC_ was aligned with the corresponding region of the _comE_, _qsrA_ distal motifs, [PERSON] and colleagues identified a single base pair that was conserved in the _blpA_ (CSP-inducible) motif, but not in the other BlpR-regulated motifs (Figure 1, inset). After mutating this base pair to that of the corresponding base pair found in all other BlpR-regulated motifs, [PERSON] et al. observed a loss of CSP-induced BIR expression [33]. Furthermore, BlpC-induced expression of the BIR remained intact, suggesting that this direct repeat could no longer accommodate ComE binding, yet still retained the ability to bind BlpR [33]. The co-evolution of competence development and bacteriocin production not only strongly implicates their parallel functions, but also suggests that the interconnection between these mechanisms provides an advantage in predation on other cells. Interestingly, a similar relationship is emerging between these two QS pathways in the oral pathogen _S. mutans_, suggesting a potentially conserved theme among competent _Streptococcus_.