Navigating Environmental Transitions: the Role of Phenotypic Variation in Bacterial Responses

ABSTRACT The ability of bacteria to respond to changes in their environment is critical to their survival, allowing them to withstand stress, form complex communities, and induce virulence responses during host infection. A remarkable feature of many of these bacterial responses is that they are often variable across individual cells, despite occurring in an isogenic population exposed to a homogeneous environmental change, a phenomenon known as phenotypic heterogeneity. Phenotypic heterogeneity can enable bet-hedging or division of labor strategies that allow bacteria to survive fluctuating conditions. Investigating the significance of phenotypic heterogeneity in environmental transitions requires dynamic, single-cell data. Technical advances in quantitative single-cell measurements, imaging, and microfluidics have led to a surge of publications on this topic. Here, we review recent discoveries on single-cell bacterial responses to environmental transitions of various origins and complexities, from simple diauxic shifts to community behaviors in biofilm formation to virulence regulation during infection. We describe how these studies firmly establish that this form of heterogeneity is prevalent and a conserved mechanism by which bacteria cope with fluctuating conditions. We end with an outline of current challenges and future directions for the field. While it remains challenging to predict how an individual bacterium will respond to a given environmental input, we anticipate that capturing the dynamics of the process will begin to resolve this and facilitate rational perturbation of environmental responses for therapeutic and bioengineering purposes.