Response of single bacterial cells to stress gives rise to complex history dependence at the population level

Abstract

Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure.bacterial memory | single cell | cell cycle | priming | synchronization B acteria are constantly challenged by their environment (1). Are bacterial cells able to respond better to environmental changes if they have experienced similar conditions in the recent past? It has been demonstrated that bacterial populations respond faster to a change of nutrient source when the forthcoming nutrient source has been presented in the recent past (2, 3). Similarly, bacterial populations that were exposed to sublethal stress levels showed increased survival of a higher stress level of the same type (4-6). Theoretical and experimental studies indicate that basing cellular decisions on environmental cues perceived in the past can be advantageous in dynamic environments (3,7,8), suggesting that such history-dependent behavior can be the result of adaptive evolution in dynamic environments.In this study we addressed the question of memory on a singlecell level. We asked whether weak stress events provide individual cells with increased tolerance against future stress. Memory effects usually have been studied on the basis of population measurements (4, 9-12). Using population measurements, it is difficult to determine whether history dependence is a consequence of the behavioral changes in individuals or of a shift in the composition of the population as a result of past events. By using single-cell analysis, we investigated how the behavior of individuals scaled up to hi...

History of Antibiotic Adaptation Influences Microbial Evolutionary Dynamics During Subsequent Treatment

“…More broadly, mechanisms of memory and history dependence in bacterial systems are being uncovered to better understand the dynamics of bacterial survival and adaptation in changing environments [69][70][71]. For example, a recent study showed that the survival of Caulobacter crescentus in response to a high concentration of sodium chloride stress depended on the duration and timing of an earlier treatment of a moderate concentration of sodium chloride and that this effect was linked to delays in cell division, which led to cell-cycle synchronization [72]. Another study described what they call response memory, which is when a gene regulatory network continues to persist after the removal of its external inducer.…”

Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System

“…"Memory" of stress responses has been reported for different aspects of cellular adaptations to stress conditions (38)(39)(40). The timing of growth resumption from stationary phase has been discovered to correlate with the timing of entry into stationary phase, although the molecular mechanism of this phenomenon has not been elucidated (40).…”

The Swiss Society of Microbiology: Small Bugs, Big Questions and Cool Answers

“…In a similar approach Mathis et al also traced the Caulobacter cell history by live cell imaging in microfluidic devices after salt stress to monitor the history-dependence of bacterial stress responses. [20] They observed the emergence of memorylike behaviour at the level of the population, indicating that past events can indeed modulate the behavioural traits of individuals and groups of bacteria.…”