Phenotypic heterogeneity in the bacterial oxidative stress response is driven by cell-cell interactions

Genetically identical bacterial cells commonly display different phenotypes. This phenotypic heterogeneity is well known for stress responses, where it is often explained as bet hedging against unpredictable environ-mental threats. Here, we explore phenotypic heterogeneity in a major stress response of Escherichia coli and find it has a fundamentally different basis. We characterize the response of cells exposed to hydrogen peroxide (H2O2) stress in a microfluidic device under constant growth conditions. A machine-learning model reveals that phenotypic heterogeneity arises from a precise and rapid feedback between each cell and its im-mediate environment. Moreover, we find that the heterogeneity rests upon cell-cell interaction, whereby cells shield each other from H2O2 via their individual stress responses. Our work shows how phenotypic hetero-geneity in bacterial stress responses can emerge from short-range cell-cell interactions and result in a col-lective phenotype that protects a large proportion of the population.

Automated summary

Genetically identical bacterial cells often exhibit different phenotypes, which is commonly explained as a bet-hedging strategy against unpredictable environmental threats. However, this study reveals that phenotypic heterogeneity in Escherichia coli's stress response to hydrogen peroxide stress has a fundamentally different basis. Through microfluidic experiments, it is found that the heterogeneity arises from precise and rapid feedback between individual cells and their immediate environment. Furthermore, cell-cell interactions play a crucial role in shielding each other from hydrogen peroxide, resulting in a collective phenotype that protects a significant portion of the population.