Control of natural transformation in salivarius Streptococci through specific degradation of σX by the MecA-ClpCP protease complex.
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 system in the salivarius species Streptococcus thermophilus. Using in vitro approaches, we showed that MecA specifically interacts with both σ(X) and ClpC, suggesting the formation of a ternary σ(X)-MecA-ClpC complex. Moreover, we demonstrated that MecA ultimately targets σ(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 σ(X) as essential for the interaction with MecA and subsequent σ(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 σ(X) activity is proposed.
Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Astrid
A
Wahl
Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Florence
F
Servais
Université Lille Nord de France and UDSL, Plate-Forme d'Interactions Moléculaires, IMPRT, IFR 114, Faculté de Médecine, Lille, France.
Anne-Sophie
AS
Drucbert
Université Lille Nord de France and UDSL, EA-4481, UFR Pharmacie, Lille, France.
Catherine
C
Foulon
Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium laetitia.fontaine@uclouvain.be pascal.hols@uclouvain.be.
Laetitia
L
Fontaine
Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium laetitia.fontaine@uclouvain.be pascal.hols@uclouvain.be.
Pascal
P
Hols
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D061269:DNA Transformation Competence / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D048249:Streptococcus thermophilus / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014169:Transformation, Bacterial
D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; C120829:ComX protein, Streptococcus; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D012808:Sigma Factor; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C118340:ClpE protein, bacteria