Repository logo

Tunable phenotypic variability through an autoregulatory alternative sigma factor circuit

Published version

Change log


Schwall, Christian P 
Loman, Torkel E 
Martins, Bruno M C 
Cortijo, Sandra 
Villava, Casandra 


Abstract: Genetically identical individuals in bacterial populations can display significant phenotypic variability. This variability can be functional, for example by allowing a fraction of stress prepared cells to survive an otherwise lethal stress. The optimal fraction of stress prepared cells depends on environmental conditions. However, how bacterial populations modulate their level of phenotypic variability remains unclear. Here we show that the alternative sigma factor σV circuit in Bacillus subtilis generates functional phenotypic variability that can be tuned by stress level, environmental history and genetic perturbations. Using single‐cell time‐lapse microscopy and microfluidics, we find the fraction of cells that immediately activate σV under lysozyme stress depends on stress level and on a transcriptional memory of previous stress. Iteration between model and experiment reveals that this tunability can be explained by the autoregulatory feedback structure of the sigV operon. As predicted by the model, genetic perturbations to the operon also modulate the response variability. The conserved sigma‐anti‐sigma autoregulation motif is thus a simple mechanism for bacterial populations to modulate their heterogeneity based on their environment.


Funder: FP7 Ideas: European Research Council (FP7 Ideas); Id:; Grant(s): 338060


EMBO23, Article, Articles, Bacillus subtilis, microbial systems biology, single‐cell time‐lapse microscopy, stochastic gene expression, stress priming

Journal Title

Molecular Systems Biology

Conference Name

Journal ISSN


Volume Title



Gatsby Charitable Foundation (GAT3272/GLC)
EC | H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska‐Curie Actions (MSCA) (721456)