A delivered DNase toxin creates population heterogeneity through transient intoxication of siblings.

Population heterogeneity is important for multicellular behavior, as well as bet-hedging strategies. Recent findings suggest a role for bacterial toxin delivery in generating population heterogeneity, but the molecular mechanisms by which this occurs are not well understood. Here, we address IMPORTANCE: Population heterogeneity is important for multicellularity, as well as for bet-hedging strategies. A heterogeneous population allows cells with the same genotype to respond differently to environmental cues and stresses. For multicellularity, heterogeneity originates from coordinated signaling, whereas bet-hedging strategies can arise stochastically due to cell-to-cell variation in the concentration of signaling molecules. However, recent advances suggest a role for bacterial toxin delivery in the generation of population heterogeneity. How toxins mediate heterogeneity mechanistically is, however, unclear. Here, we show that kin cells transiently intoxicate each other with CdiA toxins, resulting in physiological changes. These changes are specific to the toxic activity, i.e., other toxins with different activities are likely to give rise to other responses. Thus, we find that the arsenal of toxins that bacteria harbor could affect their ability to participate in bet-hedging strategies, as well as in multicellular behavior.