Hpr (ScoC) and the phosphorelay couple cell cycle and sporulation in Bacillus subtilis

Bacillus subtilis sporulation is a developmental process that culminates in the formation of a highly resistant and persistent endospore. Inhibiting DNA synthesis prior to the completion of the final round of DNA replication blocks sporulation at an early stage. Conditions that prevent compartmentalization of gene expression, i.e. inhibition of asymmetric septum formation or chromosome partitioning, also block sporulation at an early stage. Multiple mechanisms including a RecA-dependent, a RecA-independent, and the soj-spo0J operon have been implicated in signal transduction, connecting DNA replication and chromosome partitioning to the onset of sporulation in B. subtilis. We suggest that a single mechanism involving Hpr (ScoC) and Sda couple cell cycle signaling to sporulation initiation. We show that transcription of phosphorelay sensory chain genes is adversely affected by post-exponential perturbation of the cell cycle. DNA replication arrest by chemical treatments, such as hydroxyphenylazouracil, hydroxyurea, nalidixic acid, and through genetic means using dnaA1ts and dnaB19ts temperature-sensitive mutants caused substantial down-regulation of spo0F and kinA expression and elevated the expression of spo0A and spo0H (sigH). Despite the elevation in spo0A expression, Spo0A approximately P-dependent sinI expression was substantially down-regulated indicating that in vivo Spo0A approximately P levels may be diminished. Similar alterations in gene expression patterns were observed in an ftsA279ts mutant background, indicating that cytokinesis and sporulation may also be coupled by a similar mechanism. Loss of function mutation in hpr (scoC) restored sporulation in a dnaA1ts mutant, blocked the DNA replication arrest induction of spo0A expression and restored expression of spo0F, kinA and sinI. Moreover, hpr expression was up-regulated in response to DNA replication arrest. The increase in hpr expression required Sda. These results suggest a role for Hpr (ScoC) in mediating the coupling of cell cycle events to the onset of sporulation.