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Narula, Jatin; Kuchina, Anna; Zhang, Fang; Fujita, Masaya; Süel, Gürol M; Igoshin, Oleg A
Molecular systems biology, 20/May , Letnik: 12, Številka: 5Journal Article
How can changes in growth rate affect the regulatory networks behavior and the outcomes of cellular differentiation? We address this question by focusing on starvation response in sporulating Bacillus subtilis. We show that the activity of sporulation master regulator Spo0A increases with decreasing cellular growth rate. Using a mathematical model of the phosphorelay—the network controlling Spo0A—we predict that this increase in Spo0A activity can be explained by the phosphorelay protein accumulation and lengthening of the period between chromosomal replication events caused by growth slowdown. As a result, only cells growing slower than a certain rate reach threshold Spo0A activity necessary for sporulation. This growth threshold model accurately predicts cell fates and explains the distribution of sporulation deferral times. We confirm our predictions experimentally and show that the concentration rather than activity of phosphorelay proteins is affected by the growth slowdown. We conclude that sensing the growth rates enables cells to indirectly detect starvation without the need for evaluating specific stress signals. Synopsis The phosphorelay network controlling sporulation in Bacillus subtilis responds to starvation by sensing the slowdown of in cellular growth. Growth rate sensing enables indirect detection of starvation without specific nutrient‐sensing mechanisms. Slowdown of growth during starvation leads to accumulation of proteins of the phosphorelay network and longer intervals between DNA replication cycles. These effects increase the activity of master regulator Spo0A. Only cells growing with a rate slower than a certain threshold reach the Spo0A activity necessary for sporulation. Growth‐rate‐dependent increase in Spo0A activity is responsible for the multi‐generation deferral of sporulation during starvation. The concentration rather than activity of phosphorelay proteins is affected by the growth slowdown. The phosphorelay network controlling sporulation in Bacillus subtilis responds to starvation by sensing the slowdown of in cellular growth. Growth rate sensing enables indirect detection of starvation without specific nutrient‐sensing mechanisms.
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