Dataset Information

Control of natural transformation in salivarius Streptococci through specific degradation of ?X by the MecA-ClpCP protease complex.

ABSTRACT: Competence for natural DNA transformation is a tightly controlled developmental process in streptococci. In mutans and salivarius species, the abundance of the central competence regulator ?(X) is regulated at two levels: transcriptional, by the ComRS signaling system via the ?(X)/ComX/SigX-inducing peptide (XIP), and posttranscriptional, by the adaptor protein MecA and its associated Clp ATPase, ClpC. In this study, we further investigated the mechanism and function of the MecA-ClpC control system in the salivarius species Streptococcus thermophilus. Using in vitro approaches, we showed that MecA specifically interacts with both ?(X) and ClpC, suggesting the formation of a ternary ?(X)-MecA-ClpC complex. Moreover, we demonstrated that MecA ultimately targets ?(X) for its degradation by the ClpCP protease in an ATP-dependent manner. We also identify a short sequence (18 amino acids) in the N-terminal domain of ?(X) as essential for the interaction with MecA and subsequent ?(X) degradation. Finally, increased transformability of a MecA-deficient strain in the presence of subinducing XIP concentrations suggests that the MecA-ClpCP proteolytic complex acts as an additional locking device to prevent competence under inappropriate conditions. A model of the interplay between ComRS and MecA-ClpCP in the control of ?(X) activity is proposed.

SUBMITTER: Wahl A

PROVIDER: S-EPMC4135673 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Control of natural transformation in salivarius Streptococci through specific degradation of σX by the MecA-ClpCP protease complex.

Wahl Astrid A Servais Florence F Drucbert Anne-Sophie AS Foulon Catherine C Fontaine Laetitia L Hols Pascal P

Journal of bacteriology 20140516 15

Competence for natural DNA transformation is a tightly controlled developmental process in streptococci. In mutans and salivarius species, the abundance of the central competence regulator σ(X) is regulated at two levels: transcriptional, by the ComRS signaling system via the σ(X)/ComX/SigX-inducing peptide (XIP), and posttranscriptional, by the adaptor protein MecA and its associated Clp ATPase, ClpC. In this study, we further investigated the mechanism and function of the MecA-ClpC control sys ...[more]

PMID: 24837292

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Project description:In bacteria, phenotypic heterogeneity rescues the need for diversity in isogenic populations and allow concomitant multiple survival strategies when choosing only one is too risky. This powerful tactic is exploited for competence in streptococci and results in a bimodal activation, where only a subset of the community triggers the system. Deciphering the mechanisms underlying this puzzling behavior has remained challenging, especially since its study has been mainly achieved in S. mutans, where two different but interconnected regulation networks control competence. In this work, we sought to determine the origin of bimodality associated to the ComRS system thanks to the simplified S. salivarius model that harbors no supplemental signaling system. Using a single cell fluorescence reporter system together with the overexpression of the main actors of the regulation network, we showed that the ComR intracellular concentration is directly linked to the proportion of competent cells in the population. We report that this type of activation requires a functional positive feedback loop acting on comS through Opp and a putative ComS exporter, PptAB. To determine the origin of the heterogeneity amplified by the loop, we developed a mathematical model suggesting that either noise on ComS or ComR abundance could explain bimodality. Because ComR abundance is central for competence bimodal activation, we conducted an in silico identification and a systematic deletion of all the Two Component Systems (TCS) present in S. salivarius and identified CovRS, a well described virulence regulator in GAS and GBS, as a repressor of comR transcription. In vitro direct binding of CovR with the promoter of comR and transcriptomics confirmed those data. As CovRS integrates environmental stimuli that control ComR intracellular concentration, it represents the missing puzzle piece bridging environmental conditions and competence (bimodal) activation in salivarius streptococci.

Dataset Information

Control of natural transformation in salivarius Streptococci through specific degradation of ?X by the MecA-ClpCP protease complex.

Publications

Control of natural transformation in salivarius Streptococci through specific degradation of σX by the MecA-ClpCP protease complex.

Similar Datasets

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