A novel double‐tryptophan peptide pheromone controls competence in Streptococcus spp. via an Rgg regulator

Abstract

SummaryAll streptococcal genomes encode the alternative sigma factor SigX and 21 SigX-dependent proteins required for genetic transformation, yet no pyogenic streptococci are known to develop competence. Resolving this paradox may depend on understanding the regulation of sigX. We report the identification of a regulatory circuit linked to the sigX genes of mutans, pyogenic, and bovis streptococci that uses a novel small, double-tryptophan-containing sigX-inducing peptide (XIP) pheromone. In all three groups, the XIP gene (comS), and sigX have identical, non-canonical promoters consisting of 9 bp inverted repeats separated from a -10 hexamer by 19 bp. comS is adjacent to a gene encoding a putative transcription factor of the Rgg family and is regulated by its product, which we designate ComR. Deletion of comR or comS in Streptococcus mutans abolished transformability, as did deletion of the oligopeptide permease subunit oppD, suggesting that XIP is imported. Providing S. mutans with synthetic fragments of ComS revealed that seven C-terminal residues, including the WW motif, cause robust induction of both sigX and the competent state. We propose that this circuit is the proximal regulator of sigX in S. mutans, and we infer that it controls competence in a parallel way in all pyogenic and bovis streptococci.

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

“…The quorum sensing system of streptococci has encountered a paradigm shift in recent years owing to the discovery of a novel competence-inducing peptide, termed XIP, the proximal response regulator comR and the gene for the synthesis of the XIP precursor comS, all of which are highly conserved in streptococci (Mashburn-Warren et al, 2010;Fontaine et al, 2013). In S. mutans, the heptapeptide XIP induces competence in an unimodal way, whereas the previously studied CSP induces competence only in a fraction of the cells while the majority remains uninduced and a small subpopulation undergoes autolysis (Lemme et al, 2011;Dufour and Levesque, 2013).…”

“…S. mutans secretes the so-called AI-2, for which no signalling function could so far be identified in this organism (Sztajer et al, 2008). It also secretes two peptide pheromones, the CSP (Li et al, 2001) and XIP (alternative sigma factor sigX-inducing peptide) (Mashburn-Warren et al, 2010;Khan et al, 2012) that induce genetic competence through two different signalling pathways converging on SigX, the only alternative sigma factor of S. mutans, which is therefore a master regulator of quorum sensing .…”

Transcriptome analysis reveals that ClpXP proteolysis controls key virulence properties of Streptococcus mutans

“…Among the known competence genes found to be downregulated were the sigma factor comX, several genes of the late competence comY operon and the newly described comR transcriptional regulator (Mashburn-Warren et al, 2010). We assessed the transformation efficiency of DclpP and DclpX with and without the addition of exogenous CSP.…”

Streptococcus mutans: a new Gram-positive paradigm?

“…Streptococcus salivarius, Streptococcus thermophilus), which led to the development of protocols for in vitro transformation of S. salivarius and S. thermophilus (Fontaine et al, 2010). Remarkably, 'non-transformable' members of the pyogenic and bovis groups of streptococci also possess a regulatory system homologous to ComR/ ComS (Mashburn-Warren et al, 2010).…”

“…Despite an overlap with competence-related gene expression, the CSP regulatory circuit was later found to be dispensable for S. mutans competence and was implicated in non-lantibiotic bacteriocin production (Ahn et al, 2006;Kreth et al, 2005;Mashburn-Warren et al, 2010). Using a microfluidic, singlecell method, Son et al (2012) provided novel clues on how S. mutans responds to extracellular signals to activate ComX.…”