A Novel Pheromone Quorum-Sensing System Controls the Development of Natural Competence in
            <i>Streptococcus thermophilus</i>
            and
            <i>Streptococcus salivarius</i>

Fontaine, Laetitia; Boutry, Céline; Frahan, Marie Henry de; Delplace, Brigitte; Fremaux, Christophe; Horvath, Philippe; Boyaval, Patrick; Hols, Pascal

doi:10.1128/jb.01251-09

Cited by 208 publications

(349 citation statements)

References 55 publications

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“…observed, pointing out their important role in adaptative and virulence processes (27)(28)(29)(30)(31)(32). This clearly identifies these regulators as major targets for the search of new molecules with applications in medical, food, and biotechnology areas.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Grenha

Slamti

Nicaise

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria. To fully understand the activation mechanism of PlcR, we took a closer look at the conformation changes induced upon binding of PapR and of its target DNA, known as PlcR-box. For that purpose we have determined the structures of the apoform of PlcR (Apo PlcR) and of the ternary complex of PlcR with PapR and the PlcR-box from the plcA promoter. Comparison of the apoform of PlcR with the previously published structure of the PlcR-PapR binary complex shows how a small conformational change induced in the C-terminal region of the tetratricopeptide repeat (TPR) domain upon peptide binding propagates via the linker helix to the N-terminal HTH DNA-binding domain. Further comparison with the PlcR-PapR-DNA ternary complex shows how the activation of the PlcR dimer allows the linker helix to undergo a drastic conformational change and subsequent proper positioning of the HTH domains in the major groove of the two half sites of the pseudopalindromic PlcR-box. Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch

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Section: Discussionmentioning

confidence: 99%

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Grenha

Slamti

Nicaise

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, S. thermophilus was shown to be able to develop natural competence for transformation, a transitory physiological state enabling the capture and stable integration of naked DNA in the chromosome of this species (2,14,15,18).…”

mentioning

confidence: 99%

“…For S. thermophilus, competence was shown to be naturally induced when S. thermophilus cells were grown in a chemically defined medium. This induction results in the transitory expression of the comX gene, coding for the master regulator of late competence (com) genes, which are necessary for DNA uptake, protection, and chromosomal integration (14,18). ComX is an alternative sigma factor ( X ) that binds to the RNA polymerase in order to transcribe specifically the late com genes by recognizing a small sequence (Com box) in their upstream regions (31,33,46).…”

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confidence: 99%

Adaptor Protein MecA Is a Negative Regulator of the Expression of Late Competence Genes in Streptococcus thermophilus

et al. 2012

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In Streptococcus thermophilus, the ComRS regulatory system governs the transcriptional level of comX expression and, hence, controls the early stage of competence development. The present work focuses on the posttranslational control of the activity of the sigma factor ComX and, therefore, on the late stage of competence regulation. In silico analysis performed on the S. thermophilus genome revealed the presence of a homolog of mecA (mecA St ), which codes for the adaptor protein that is involved in ComK degradation by ClpCP in Bacillus subtilis. Using reporter strains and microarray experiments, we showed that MecA St represses late competence genes without affecting the early competence stage under conditions that are not permissive for competence development. In addition, this repression mechanism was found not only to act downstream of comX expression but also to be fully dependent on the presence of a functional comX gene. This negative control was similarly released in strains deleted for clpC, mecA, and clpC-mecA. Under artificial conditions of comX expression, we next showed that the abundance of ComX is higher in the absence of MecA or ClpC. Finally, results of bacterial two-hybrid assays strongly suggested that MecA interacts with both ComX and ClpC. Based on these results, we proposed that ClpC and MecA act together in the same regulatory circuit to control the abundance of ComX in S. thermophilus.

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“…More recently, a novel double-tryptophan peptide known as sigX-inducing peptide (XIP, encoded by comS) and an Rgg-type regulator (designated comR) responsible for inducing comX expression were identified in members of the salivarius group (e.g. 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).…”

Section: S Mutans Is the Bacterial Paradigm Of Lactic Acid Bacteria mentioning

confidence: 99%

Streptococcus mutans: a new Gram-positive paradigm?

et al. 2013

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Despite the enormous contributions of the bacterial paradigms Escherichia coli and Bacillus subtilis to basic and applied research, it is well known that no single organism can be a perfect representative of all other species. However, given that some bacteria are difficult, or virtually impossible, to cultivate in the laboratory, that some are recalcitrant to genetic and molecular manipulation, and that others can be extremely dangerous to manipulate, the use of model organisms will continue to play an important role in the development of basic research. In particular, model organisms are very useful for providing a better understanding of the biology of closely related species. Here, we discuss how the lifestyle, the availability of suitable in vitro and in vivo systems, and a thorough understanding of the genetics, biochemistry and physiology of the dental pathogen Streptococcus mutans have greatly advanced our understanding of important areas in the field of bacteriology such as interspecies biofilms, competence development and stress responses. In this article, we provide an argument that places S. mutans, an organism that evolved in close association with the human host, as a novel Gram-positive model organism.Advances in the field of bacteriology have relied strongly on studies involving the bacterial paradigms Escherichia coli and Bacillus subtilis. In both cases, a long history of laboratory research, ease of cultivation and genetic manipulation encouraged and provided the rationale for the emergence of these bacteria as model organisms. E. coli is a Gramnegative, non-sporulating bacterium that can be found freeliving, in water or soil, as well as associated with plants, insects, birds and mammals. It is the most studied prokaryotic organism and comprises a very heterogeneous group containing both pathogenic and non-pathogenic strains. In addition to serving as the Gram-negative model organism, laboratory strains of E. coli are extremely versatile and are the quintessential lab workhorses. Bacillus subtilis is a Gram-positive sporulating organism commonly found in soil, plants and, transiently, on the surface of animals. Strains of B. subtilis are not associated with humans and are not pathogenic, although some closely related Bacillus species such as Bacillus anthracis and Bacillus cereus are implicated in human disease (anthrax) and in food poisoning, respectively. Because the sporulation process occurs in simple well-defined stages, B. subtilis sporulation has served as a paradigm for bacterial development and differentiation studies. Like E. coli, B. subtilis is also easy to cultivate and highly amenable to genetic manipulation. The wealth of information derived from investigations of the biochemistry, physiology, genetics and developmental processes of E. coli and B. subtilis laid the foundation for, and at the same time provided guidance for, studies with other bacterial species. In addition to E. coli and B. subtilis, there are numerous other organisms that have served, in a more limited scope, a...

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A Novel Pheromone Quorum-Sensing System Controls the Development of Natural Competence in Streptococcus thermophilus and Streptococcus salivarius

Cited by 208 publications

References 55 publications

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Adaptor Protein MecA Is a Negative Regulator of the Expression of Late Competence Genes in Streptococcus thermophilus

Streptococcus mutans: a new Gram-positive paradigm?

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