Spo0A

Spo0A is a master regulator of sporulation in endospore-forming bacteria, most notably Bacillus subtilis, and is conserved among many Firmicutes. It is a response regulator that controls the initiation of sporulation through phosphorylation in a multisite phosphorelay system. Structurally, Spo0A consists of an N-terminal receiver domain that becomes phosphorylated on a conserved aspartate residue and a C-terminal DNA-binding domain that directs transcription.

Activation occurs via a phosphorelay involving sensor kinases KinA, KinB, KinC, KinD, and KinE, which transfer phosphate through Spo0F to Spo0B and finally to Spo0A, yielding Spo0A~P. The relay is modulated by phosphatases and signaling peptides (Rap–Phr systems) that adjust Spo0A activity in response to cellular conditions and populations, thereby tuning the decision to enter sporulation.

Spo0A~P acts as a transcription factor with a dual role. At intermediate levels, it represses the stationary-phase repressor AbrB, enabling expression of genes needed for adaptation to nutrient limitation. At higher levels, it activates the sporulation program, including early sporulation genes (spoI) and genes involved in engulfment, cortex formation, and spore coat assembly. Spo0A~P also represses genes that promote vegetative growth, including comK, reducing genetic competence under sporulation conditions.

As a molecular switch, Spo0A integrates nutrient status and population-density signals to balance growth, competence, biofilm formation, and sporulation. Spo0A homologs are found across spore-forming Firmicutes and regulate sporulation and related developmental processes in diverse species.