In nature, bacteria routinely encounter stressors in their environment. These can range from environmental and nutrient changes to antibiotic introduction and interactions with invading microbial or host cells (Fig. 1a). In response, bacteria have evolved many stress resistance mechanisms and response pathways. However, what has become apparent over the past several decades is that the way bacteria cope with stresses can vary substantially across cells within a population. For example, variation in gene expression and growth rate from cell to cell can act as a bet-hedging mechanism to ensure a subset of cells survives stressful conditions [1]. One of the most familiar examples of this is bacterial persistence, where communities of genetically identical cells contain two subpopulations, one of which is killed rapidly by antibiotics, while the other remains tolerant [2]. Other response mechanisms depend on the interactions between individual cells to influence collective behavior, such as in the case of biofilm production. In addition, bacteria in nature are found in mixed species communities, which results in a myriad of effects, including competition for resources, toxin production, cross-feeding, and exchange of genetic material. What these phenomena all have in common is that single-cell-level effects play a critical role in determining population-level outcomes in response to stress.

In this review, we discuss recent progress in understanding stress tolerance mechanisms that lie at the interface of single-cell and population-level responses. Previous reviews on microbial stress response provide in-depth analyses of specific topics discussed within this paper 3, 4, 5, 6, 7, 8, 9, 10, 11. However, here, we highlight commonalities across a range of stress response mechanisms to shed light on their interconnection, focusing our discussion on recent results in the area. We begin by investigating single-cell-level responses to stressors, then discuss advances in quantifying the impact of single-cell effects on population-level behavior, including biofilm production and horizontal gene transfer. Overall, we highlight how linking single-cell and population-level mechanisms is key to understanding how microbial communities coordinate their response to stress.