Extracellular Identification of a Processed Type II ComR/ComS Pheromone of
            <i>Streptococcus mutans</i>

Khan, Rabia; Valen, Håkon; Filho, Antônio Pedro Ricomini; Fimland, Gunnar; Arntzen, Magnus Ø.; Thiede, Bernd; Petersen, Fernanda Cristina

doi:10.1128/jb.00624-12

Cited by 71 publications

(108 citation statements)

References 43 publications

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“…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 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Polymicrobial biofilms are of large medical importance, but relatively little is known about the role of interspecies interactions for their physiology and virulence. Here, we studied two human pathogens co-occuring in the oral cavity, the opportunistic fungus Candida albicans and the caries-promoting bacterium Streptococcus mutans. Dual-species biofilms reached higher biomass and cell numbers than mono-species biofilms, and the production of extracellular polymeric substances (EPSs) by S. mutans was strongly suppressed, which was confirmed by scanning electron microscopy, gas chromatography-mass spectrometry and transcriptome analysis. To detect interkingdom communication, C. albicans was co-cultivated with a strain of S. mutans carrying a transcriptional fusion between a green fluorescent protein-encoding gene and the promoter for sigX, the alternative sigma factor of S. mutans, which is induced by quorum sensing signals. Strong induction of sigX was observed in dual-species biofilms, but not in single-species biofilms. Conditioned media from mixed biofilms but not from C. albicans or S. mutans cultivated alone activated sigX in the reporter strain. Deletion of comS encoding the synthesis of the sigX-inducing peptide precursor abolished this activity, whereas deletion of comC encoding the competence-stimulating peptide precursor had no effect. Transcriptome analysis of S. mutans confirmed induction of comS, sigX, bacteriocins and the downstream late competence genes, including fratricins, in dual-species biofilms. We show here for the first time the stimulation of the complete quorum sensing system of S. mutans by a species from another kingdom, namely the fungus C. albicans, resulting in fundamentally changed virulence properties of the caries pathogen.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…The first class, used by the mitis and anginosus groups, is sensed by a two-component system comprising a histidine kinase (ComD) that binds the extracellular cognate CSPs, leading to the phosphorylation of the response regulator ComE [4,5]. The XIP class is used by most other streptococci, and is transported inside the cells by Opp oligopeptide permeases, leading to the activation of intracellular Rgg-type regulators [6,7,8,9]. The last class, comprising bacteriocin-inducing peptides, is only known in S. mutans.…”

Section: Introductionmentioning

confidence: 99%

Natural Transformation of Oral Streptococci by Use of Synthetic Pheromones

Salvadori

Junges

Khan

et al. 2016

Methods in Molecular Biology

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The discovery that Streptococcus pneumoniae uses a competence-stimulating peptide (CSP) to induce competence for natural transformation, and that other species of the mitis and the anginosus streptococcal groups use a similar system, has expanded the tools to explore gene function and regulatory pathways in streptococci. Two other classes of pheromones have been discovered since then, comprising the bacteriocin-inducing peptide class found in Streptococcus mutans (also named CSP, although different from the former) and the SigX-inducing peptides (XIP), in the mutans, salivarius, bovis, and pyogenes groups of streptococci. The three classes of peptide pheromones can be ordered from peptide synthesis services at affordable prices, and used in transformation assays to obtain competent cultures consistently at levels usually higher than those achieved during spontaneous competence. In this chapter, we present protocols for natural transformation of oral streptococci that are based on the use of synthetic pheromones, with examples of conditions optimized for transformation of S. mutans and Streptococcus mitis.

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“…This missing link has recently been filled by the identification of the type II ComRS signaling system that directly controls the transcription of comX in S. mutans in response to XIP (10). When S. mutans is grown in a chemically defined medium (CDM) with the addition of synthetic XIP, competence activation through the ComRS signaling system is superior, involving nearly the entire population (10,18,19). However, XIP appears to be inactive and only CSP induces competence when S. mutans is grown in a complex medium (18,20).…”

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confidence: 99%

MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

et al. 2013

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c Streptococcus mutans develops competence for genetic transformation through a complex network that receives inputs from at least two signaling peptides, competence-stimulating peptide (CSP) and sigX-inducing peptide (XIP). The key step of competence induction is the transcriptional activation of comX, which encodes an alternative sigma factor, SigX ( X ), controlling the expression of late competence genes essential for DNA uptake and recombination. In this study, we provide evidence that MecA acts as a negative regulator in the posttranslational regulation of SigX in S. mutans. Using luxAB transcriptional reporter strains, we demonstrate that MecA represses the expression of late competence genes in S. mutans grown in a complex medium that is subpermissive for competence induction by CSP. The negative regulation of competence by MecA requires the presence of a functional SigX. Accordingly, inactivation of MecA results in a prolonged competence state of S. mutans under this condition. We have also found that the AAA؉ protease ClpC displays a similar repressing effect on late competence genes, suggesting that both MecA and ClpC function coordinately to regulate competence in the same regulatory circuit in S. mutans. This suggestion is strongly supported by the results of bacterial two-hybrid assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that inactivation of MecA or ClpC results in the intracellular accumulation of the SigX in S. mutans. Together, our data support the notion that MecA mediates the formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby negatively regulates genetic competence in S. mutans.

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Extracellular Identification of a Processed Type II ComR/ComS Pheromone of Streptococcus mutans

Cited by 71 publications

References 43 publications

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

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

Natural Transformation of Oral Streptococci by Use of Synthetic Pheromones

MecA Protein Acts as a Negative Regulator of Genetic Competence in Streptococcus mutans

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