Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Mol Syst Biol. 2012;8:626. doi: 10.1038/msb.2012.57.
Programmed death is often associated with a bacterial stress response. This behavior appears paradoxical, as it offers no benefit to the individual. This paradox can be explained if the death is 'altruistic': the killing of some cells can benefit the survivors through release of 'public goods'. However, the conditions where bacterial programmed death becomes advantageous have not been unambiguously demonstrated experimentally. Here, we determined such conditions by engineering tunable, stress-induced altruistic death in the bacterium Escherichia coli. Using a mathematical model, we predicted the existence of an optimal programmed death rate that maximizes population growth under stress. We further predicted that altruistic death could generate the 'Eagle effect', a counter-intuitive phenomenon where bacteria appear to grow better when treated with higher antibiotic concentrations. In support of these modeling insights, we experimentally demonstrated both the optimality in programmed death rate and the Eagle effect using our engineered system. Our findings fill a critical conceptual gap in the analysis of the evolution of bacterial programmed death, and have implications for a design of antibiotic treatment.
程序性死亡通常与细菌应激反应有关。这种行为似乎自相矛盾,因为它对个体没有任何好处。如果死亡是“利他的”,那么这种悖论就可以得到解释:一些细胞的死亡可以通过释放“公共物品”使幸存者受益。然而,细菌程序性死亡变得有利的条件尚未在实验中得到明确证明。在这里,我们通过对细菌大肠杆菌进行可调节的、应激诱导的利他性死亡工程设计来确定这种条件。我们使用数学模型预测了在应激下最大化种群生长的最优程序性死亡率的存在。我们进一步预测,利他性死亡可以产生“鹰效应”,这是一种反直觉的现象,即在更高的抗生素浓度下处理细菌时,细菌似乎生长得更好。为了支持这些建模见解,我们使用我们的工程系统实验证明了程序性死亡率的最优性和鹰效应。我们的发现填补了细菌程序性死亡进化分析中的一个关键概念空白,并对抗生素治疗的设计具有重要意义。