An overarching theme of cellular regulation in bacteria arises from the trade-off between growth and stress resilience. In addition, the formation of biofilms contributes to stress survival, since these dense multicellular aggregates, in which cells are embedded in an extracellular matrix of self-produced polymers, represent a self-constructed protective and homeostatic 'niche'. As shown here for the model bacterium Escherichia coli, the inverse coordination of bacterial growth with survival and the transition to multicellularity is achieved by a highly integrated regulatory network with several sigma subunits of RNA polymerase and a small number of transcriptional hubs as central players. By conveying information about the actual (micro)environments, nucleotide second messengers such as cAMP, (p)ppGpp, and in particular c-di-GMP are the key triggers and drivers that promote either growth or stress resistance and organized multicellularity in a world of limited resources.
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