The stationary phase regulator CpcR controls cell differentiation and cry gene expression in Bacillus thuringiensis

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English. A challenge in bacterial developmental biology is to understand the mechanisms underlying cell fate. Phenotypic heterogeneity within an isogenic population allows specialization of subpopulations and a division of labor which may contribute to the survival of a group of bacteria under unfavorable conditions. Bacillus thuringiensis (Bt) is a spore-forming bacterium closely related to Bacillus anthracis, the agent of anthrax, and to Bacillus cereus, a foodborne pathogen. The feature that distinguishes Bt from its relatives is its ability to produce insecticidal toxin inclusions in sporulating cells. We recently reported that strain Bt LM1212 presents two subpopulations during stationary phase: spore-formers and crystal-producers. This feature provides this strain with a fitness advantage when in competition with a typical Bt strain that produces spores and crystals in the same cell. Here, we identified and characterized the transcriptional regulator CpcR responsible for this phenotype and for the expression of the cry toxin genes. This transcription factor belongs to the OmpR family of two-component response regulators; however, it appears that it might be atypical. We showed that cpcR transcription is autoregulated, and a search in the promoter region of the LM1212 cry and cpcR gene promoters revealed the presence of a conserved DNA sequence upstream from the -35 box. We also showed that CpcR was able to direct the production of a crystal consisting of a heterologous insecticidal Cry protein in non-sporulating cells of a typical Bt strain. Moreover, its expression induced a strong reduction in sporulation. The involvement of CpcR in the sporulation regulatory networks may provide interesting data for a better understanding of the processes occurring during the stationary phase of Bacillus species.