Abstract
Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions.
Highlights
In their natural habitats, bacteria constantly adapt to changing environmental conditions while simultaneously anticipating further disturbances
We report that in the Gram-positive model bacterium Bacillus subtilis a small regulatory RNA can induce heterogeneity in growth rates by increasing cell-to-cell variation in the levels of the transcriptional regulator AbrB, which is important for rapid growth
To efficiently cope with these changes, intricate interlinked metabolic and genetic regulation has evolved [1]. This complex regulatory network includes the action of small regulatory RNAs [2]. sRNAs are a widespread means for bacterial cells to coordinate responses by fine-tuning levels of mRNAs or proteins, and they have been studied in great detail in Gram-negative bacteria [3]
Summary
Bacteria constantly adapt to changing environmental conditions while simultaneously anticipating further disturbances. To efficiently cope with these changes, intricate interlinked metabolic and genetic regulation has evolved [1]. This complex regulatory network includes the action of small regulatory RNAs (sRNAs) [2]. Owing to the complexity of sRNA regulation, only a relatively small number of studies have focused on the physiological necessity of sRNA-target interactions. This is again true for Gram-positive bacteria, such as B. subtilis, despite the fact that many potential sRNAs have been identified [8, 9]
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