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bioRxiv · 10.1101/2022.07.07.499079

The slowdown of growth rate controls the single-cell distribution of biofilm matrix production via a SinI-SinR-SlrR network

Chen, Z.·Zarazua-Osorio, B.·Srivastava, P.·Fujita, M.·Igoshin, O. A.
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Abstract

In Bacillus subtilis, a master regulator Spo0A controls several cell-differentiation pathways. Under moderate starvation, phosphorylated Spo0A (Spo0A~P) induces biofilm formation by indirectly activating genes controlling matrix production in a subpopulation of cells via a SinI-SinR-SlrR network. Under severe starvation, Spo0A~P induces sporulation by directly and indirectly regulating sporulation gene expression. However, what determines the heterogeneity of individual cell fates is not fully understood. In particular, it is still unclear why, despite being controlled by a single master regulator, biofilm matrix production and sporulation are mutually exclusive on a single-cell level. In this work, with mathematical modeling, we showed that the fluctuations in the growth rate and the intrinsic noise amplified by the bistability in the SinI-SinR-SlrR network could explain the single-cell distribution of matrix production. Moreover, we predicted an incoherent feed-forward loop: the decrease in the cellular growth rate activates matrix production by increasing in Spo0A phosphorylation level but represses it via changing the relative concentrations of SinR and SlrR. Experimental data provide evidence to support model predictions. In particular, we demonstrate how the degree to which matrix production and sporulation appear mutually exclusive is affected by genetic perturbations. ImportanceThe mechanisms of cell-fate decisions are fundamental to our understanding of multicellular organisms and bacterial communities. However, even for the best-studied model systems we still lack a complete picture of how phenotypic heterogeneity of genetically identical cells is controlled. Here, using B. subtilis as a model system, we employ a combination of mathematical modeling and experiments to explain the population-level dynamics and single-cell level heterogeneity of biofilm gene expression. The results demonstrate how the two cell fates, biofilm matrix production and sporulation, can appear mutually exclusive without explicitly inhibiting one another. Such a mechanism could be used in a wide range of other biological systems.

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Chen, Z., Zarazua-Osorio, B., Srivastava, P., Fujita, M., Igoshin, O. A.. 2022-07-09. The slowdown of growth rate controls the single-cell distribution of biofilm matrix production via a SinI-SinR-SlrR network. https://doi.org/10.1101/2022.07.07.499079

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