Data from: Escherichia coli populations in unpredictably fluctuating environments evolve to face novel stresses through enhanced efflux activity

There is considerable understanding about how laboratory populations respond to predictable (constant or deteriorating environment) selection for single environmental variables such as temperature or pH. However, such insights may not apply when selection environments comprise multiple variables that fluctuate unpredictably, as is common in nature. To address this issue, we grew replicate laboratory populations of Escherichia coli in nutrient broth whose pH and concentrations of salt (NaCl) and hydrogen peroxide (H2O2) were randomly changed daily. After ~170 generations, the fitness of the selected populations had not increased in any of the three selection environments. However, these selected populations had significantly greater fitness in four novel environments which have no known fitness-correlation with tolerance to pH, NaCl or H2O2. Interestingly, contrary to expectations, hypermutators did not evolve. Instead, the selected populations evolved an increased ability for energy-dependent efflux activity that might enable them to throw out toxins, including antibiotics, from the cell at a faster rate. This provides an alternate mechanism for how evolvability can evolve in bacteria and potentially lead to broad-spectrum antibiotic resistance, even in the absence of prior antibiotic exposure. Given that environmental variability is increasing in nature, this might have serious consequences for public health.

学界目前已对实验室种群在单一环境变量（如温度或pH值）的可预测选择（恒定或恶化环境）下的响应机制形成了较为充分的认知。然而，当选择环境包含多个不可预测波动的变量时（此类情况在自然环境中十分常见），这类认知可能并不适用。为解决这一问题，我们在营养肉汤中培养了多组重复的大肠杆菌(Escherichia coli)实验室种群，该肉汤的pH值、氯化钠(NaCl)与过氧化氢(H2O2)浓度每日随机变动。经过约170代培育后，经选择的种群在三种选择环境中的适应度均未得到提升。但此类经选择的种群在四种全新环境中的适应度显著更高，且目前已知这些环境与pH值、NaCl或H2O2耐受性不存在适应度相关性。值得注意的是，与预期相悖的是，种群并未演化出高突变体(hypermutators)。相反，经选择的种群演化出了更强的能量依赖性外排活性，这或许能帮助它们以更快速度将包括抗生素在内的毒素排出细胞。这为细菌可演化性的演化机制提供了一种新的路径，且即便在未预先接触抗生素的情况下，也可能导致广谱抗生素耐药性的产生。鉴于自然环境的变异性正不断加剧，这一现象或对公共卫生造成严重影响。