5d), suggesting that the ComDE system does not affect XIP signali

5d), suggesting that the ComDE system does not affect XIP signaling, once the ComRS system is activated. Competence has been observed in a number of bacteria to occur in conjunction with lysis of a subpopulation of cells (Steinmoen et al., 2002; Claverys et al., 2007; Perry et al., 2009; Lemme et al., 2011). The lysed subpopulation is thought to contribute to the genetic pool used for DNA uptake by the competent cells. Herein, we have demonstrated a role for the XIP competence peptide as potent modulator of cell death in S. mutans. Our viability assays show XIP can kill nearly 82% of the population when supplied at a concentration

of 10 μM. To our knowledge, this is the first report that demonstrates a function for XIP DNA/RNA Synthesis inhibitor as an effector of cell death. check details We further report that XIP-mediated killing works via the ComR/S system and ComX, which positions the ComR/S and ComX in a more centralized position in the killing pathway of S. mutans. Although previous reports have attributed CSP-induced lysis to an imbalance between the ComE-regulated mutacin V and its immunity protein ImmB (Perry et al., 2009; Dufour et al., 2011; Lemme et al., 2011), here we argue that competence-associated cell death in S. mutans,

is instead, largely owing to activity downstream of ComX. This is also supported by the fact that nlmC (synonyms: cipB and bsmA) encoding mutacin V also modulates comX activity, which in turn, may contribute to its killing activity (Dufour et al., 2011). We

are currently examining genes downstream of ComX stimulated by XIP that may function as killing effectors using global transcriptome analysis. Although the killing activity of CSP harbors specificity toward its parent strain (Qi et al., 2005), the spectrum of activity of XIP has yet to be determined. XIP contains a double-tryptophan (WW) motif conserved among short hydrophobic peptides of the pyogenic and bovis groups of Streptococci, located within a conserved genomic context (Mashburn-Warren et al., 2010). Similar peptides specific for Streptococcus agalactiae, Streptococcus porcinus, and Streptococcus parauberis have been shown ADAMTS5 to bear no effect on competence or growth of S. mutans, suggesting that these peptides may be specific to their parental strain (Desai et al., 2012). XIP therefore may be exploited for targeted killing of S. mutans. Our transformation and cell viability results with CSP and/or XIP in both THYE and CDM media showed that these peptides do not function optimally under the same conditions. Our transformation results are in agreement with Desai et al. (2012) who reported that titration of THB into UA159 cultures in CDM inhibited XIP-induced transformability. While they demonstrated some level of activity of XIP in 100% THB, our results showed complete inhibition of XIP in THYE. It is likely that the yeast extract in THYE is largely responsible for the inhibition observed.

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