A positive feedback loop mediated by Sigma X enhances expression of the streptococcal regulator ComR

Abstract

Natural transformation is used by bacteria to take up DNA from their surroundings and incorporate it into their genomes. Streptococci do so during a transient period of competence, triggered by pheromones that they produce, secrete and sense under conditions influenced by the environment. In Streptococcus mutans, Streptococcus suis, and species of the bovis, salivarius and pyogenic groups of streptococci, the pheromone XIP is sensed by the intra-cellular regulator ComR, that in turn activates the transcription of comS, encoding the XIP precursor, and of sigX, encoding the only known alternative sigma factor in streptococci. Although induction of comR during competence has been known for more than fifteen years, the mechanism regulating its expression remains unidentified. By a combination of directional RNA-sequencing, optimal competence conditions, stepwise deletions and marker-less genome editing, we found that SigX is the missing link in overproduction of ComR. In the absence of comR induction, both sigX expression and transformation were significantly reduced. Placing comR and comS transcripts under the control of different regulators so as to form two interlocked positive feedback circuits may enable S. mutans to fine-tune the kinetics and magnitude of the competence response according to their need.