Fig 1. The sporulation network and the action of CsfB on σ^G.

A: the main morphological stages of sporulation are represented, with the main regulatory proteins active in the indicated cells. Pd, pre-divisional cell; Mc, mother cell; Fs, forespore; Sp, mature spore. B: organization of the transcriptional network of sporulation. The broken blue lines represent cell-cell signalling pathways. First, σ^F drives production of a protein, SpoIIR, secreted to the intermembrane space. SpoIIR then activates a membrane-embedded protease that triggers the proteolytic activation of pro-σ^E [18]. σ^E and σ^F activity are required for the assembly of a cell-cell secretion system (the SpoIIQ-SpoIIIAH channel in the figure) that, following engulfment completion, allows the mother cell to nourish the isolated forespore, thus enabling continued macromoelcualr synthesis and activation of the σ^G auto-regulatory loop [67]. Lastly, σ^G controls production of a signaling protein, SpoIVB, secreted into the intermembrane space that activates the machinery responsible for the proteolytical activation of σ^K [18]. The negative feedback loop through which σ^K limits production of σ^E is omitted for simplicity. C: the panel represents the composite negative feedback loop that operates in pre-divisional cells, and possibly also in the forespore prior to engulfment completion, to prevent activation of the σ^G positive auto-regulatory loop. Transcriptional and protein-protein interactions are shown in black and red, respectively. D: a single amino acid residue in region 2.1 (purple sector) allows CsfB to discriminate between the highly similar forespore sigma factors σ^F and σ^G: N45 of B. subtilis σ^G allows binding by CsfB, whereas a glutamate at the same position precludes binding. Conversely, a glutamate at the homologous position of σ^F (E39) impedes binding by CsfB whereas an asparagine at the same position is sufficient for binding. N45 and E39 are conserved among Bacillus orthologues of σ^G and σ^F.