Competence inhibition by the XrpA peptide encoded within the comX gene of Streptococcus mutans

Mol Microbiol. 2018 Aug;109(3):345-364. doi: 10.1111/mmi.13989. Epub 2018 Jul 31.


Streptococcus mutans displays complex regulation of natural genetic competence. Competence development in S. mutans is controlled by a peptide derived from ComS (XIP); which along with the cytosolic regulator ComR controls the expression of the alternative sigma factor comX, the master regulator of competence development. Recently, a gene embedded within the coding region of comX was discovered and designated xrpA (comX regulatory peptide A). XrpA was found to be an antagonist of ComX, but the mechanism was not established. In this study, we reveal through both genomic and proteomic techniques that XrpA is the first described negative regulator of ComRS systems in streptococci. Transcriptomic and promoter activity assays in the ΔxrpA strain revealed an up-regulation of genes controlled by both the ComR- and ComX-regulons. An in vivo protein crosslinking and in vitro fluorescent polarization assays confirmed that the N-terminal region of XrpA were found to be sufficient in inhibiting ComR-XIP complex binding to ECom-box located within the comX promoter. This inhibitory activity was sufficient for decreases in PcomX activity, transformability and ComX accumulation. XrpA serving as a modulator of ComRS activity ultimately results in changes to subpopulation behaviors and cell fate during competence activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • DNA Transformation Competence* / genetics
  • DNA Transformation Competence* / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial
  • Genomics
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • Proteomics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sigma Factor / genetics
  • Sigma Factor / metabolism
  • Streptococcus mutans* / genetics
  • Streptococcus mutans* / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Bacterial Proteins
  • ComX protein, Streptococcus
  • Recombinant Proteins
  • Sigma Factor
  • Transcription Factors