Indirect Repression by Bacillus subtilis CodY via Displacement of the Activator of the Proline Utilization Operon

Proline is an efficient source of both carbon and nitrogen for many bacterial species. In Bacillus subtilis, the proline utilization pathway, encoded by the putBCP operon, is inducible by proline. Here, we show that this induction is mediated by PutR, a proline-responsive transcriptional activator of the PucR family. When other amino acids are present in the medium, proline utilization is prioritized through transient repression by CodY, a global transcriptional regulator in Gram-positive bacteria that responds to amino acid availability. CodY-mediated repression of the putBCP operon has two novel features. First, repression requires the cooperative binding of CodY to at least two adjacent motifs. Second, though CodY binds to the region that overlaps the putB promoter, repression is due to displacement of PutR rather than competition with RNA polymerase.