Role of CovR phosphorylation in gene transcription in Streptococcus mutans.
Streptococcus mutans, the primary aetiological agent of dental caries, is one of the major bacteria of the human oral cavity. The pathogenicity of this bacterium is attributed not only to the expression of virulence factors, but also to its ability to respond and adapt rapidly to the ever-changing conditions of the oral cavity. The two-component signal transduction system (TCS) CovR/S plays a crucial role in virulence and stress response in many streptococci. Surprisingly, in S. mutans the response regulator CovR appears to be an orphan, as the cognate sensor kinase, CovS, is absent in all the strains. We found that acetyl phosphate, an intracellular phosphodonor molecule known to act in signalling, might play a role in CovR phosphorylation in vivo. We also found that in vitro, upon phosphorylation by potassium phosphoramide (a high-energy phophodonor) CovR formed a dimer and showed altered electrophoretic mobility. As expected, we found that the conserved aspartic acid residue at position 53 (D53) was the site of phosphorylation, since neither phosphorylation nor dimerization was seen when an alanine-substituted CovR mutant (D53A) was used. Surprisingly, we found that the ability of CovR to act as a transcriptional regulator does not depend upon its phosphorylation status, since the D53A mutant behaved similarly to the wild-type protein in both in vivo and in vitro DNA-binding assays. This unique phosphorylation-mediated inhibition of CovR function in S. mutans sheds light on an unconventional mechanism of the signal transduction pathway.
['Khara|Pratick|P|', 'Mohapatra|Saswat Sourav|SS|', 'Biswas|Indranil|I|']
D001216:Asparagine D001426:Bacterial Proteins D003731:Dental Caries D015964:Gene Expression Regulation, Bacterial D009154:Mutation D010755:Organophosphates D010766:Phosphorylation D010797:Phthalimides D011401:Promoter Regions, Genetic D011485:Protein Binding D055503:Protein Multimerization D013295:Streptococcus mutans D014157:Transcription Factors
CovR Streptococcus mutans Two component regulator