The second messenger cyclic di-GMP (c-di-GMP) enables bacteria to rapidly respond to changes in their environment. Miller and colleagues used a biosensor to measure the levels of intracellular c-di-GMP of Salmonella enterica subsp. enterica serovar Typhimurium during infection of macrophages. Following initial phagocytosis, the intracellular c-di-GMP levels are reduced, and the authors identified three redundant sensor phosphodiesterases that were responsible for maintaining low c-di-GMP concentrations. Deletion of all three enzymes decreased survival of a population of slow-replicating bacteria during macrophage infection, and deletion of the cellulose synthase machinery restored virulence in mutant bacteria lacking enzymatic activity, which suggests that low c-di-GMP concentrations prevent the overproduction of cellulose. The authors hypothesized that glucose limitation in the intracellular environment drives the reduction of cellulose production and promotes survival.
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Petersen, E., Mills, E. & Miller, S. I. Cyclic-di-GMP regulation promotes survival of a slow-replicating subpopulation of intracellular Salmonella Typhimurium. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.1901051116 (2019)
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Du Toit, A. Reducing the second messenger. Nat Rev Microbiol 17, 335 (2019). https://doi.org/10.1038/s41579-019-0193-6
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DOI: https://doi.org/10.1038/s41579-019-0193-6