A calcium-binding protein-sigV regulatory circuit modulates stress adaptation and persistence in Caulobacter vibrioides.

Calcium (Ca²⁺) acts as a second messenger in bacterial stress responses. In Caulobacter vibrioides, the cabp gene encodes a previously uncharacterized calcium-binding protein (CaBP). In silico analysis predicted a 133-aa protein with three EF-hand motifs and an N-terminal Sec signal peptide. Consistently, CaBP exhibited a Ca²⁺-dependent mobility shift and was localized to the periplasm in a SecA-dependent manner. Transcriptional analyses revealed a non-canonical organization in which the sigV promoter lies within the cabp coding sequence, although both genes are independently transcribed. Deletion of cabp increased biomass and stationary-phase survival. Expression analyses showed that SigmaV modulates cabp, while CaBP positively affects sigV expression, forming a Ca²⁺ and pH-responsive regulatory loop. Both genes were induced by acid stress and calcium limitation. The mutant displayed altered cell asymmetry and increased extracellular matrix production. These findings identify for the first time that CaBP as a periplasmic EF-hand calcium sensor linking ionic and pH signals to SigmaV-dependent stress regulation.