Physics of Biological Systems, Institut Pasteur, 75724 Paris Cedex 15, France.
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1802-7. doi: 10.1073/pnas.1116772109. Epub 2012 Jan 17.
The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of Escherichia coli to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reconstructed from its response function to an impulse, which then controls the efficiency of bacterial motility. We introduce a method for measuring the impulse response function based on coupling microfluidic experiments and inference methods: The response function is inferred using Bayesian methods from the observed trajectories of bacteria swimming in microfluidically controlled chemical fields. The notable advantages are that the method is based on the bacterial swimming response, it is noninvasive, without any genetic and/or mechanical preparation, and assays the behavior of the whole flagella bundle. We exploit the inference method to measure responses to aspartate and α-methylaspartate--measured previously by other methods--as well as glucose, leucine, and serine. The response to the attractant glucose is shown to be biphasic and perfectly adapted, as for aspartate. The response to the attractant serine is shown to be biphasic yet imperfectly adapted, that is, the response function has a nonzero (positive) integral. The adaptation of the response to the repellent leucine is also imperfect, with the sign of the two phases inverted with respect to serine. The diversity in the bacterial population of the response function and its dependency upon the background concentration are quantified.
感知和对外界刺激做出反应的质量是生物选择性表现的基本要素。在这里,我们考虑大肠杆菌对化学刺激的反应。对于中等幅度的刺激,细菌对被感知化学物质的通用图谱的反应是从其对脉冲的反应函数重建而来的,而该脉冲则控制着细菌运动的效率。我们引入了一种基于微流控实验和推理方法来测量脉冲响应函数的方法:使用贝叶斯方法从在微流控化学场中游泳的细菌的观察轨迹中推断响应函数。该方法的显著优点是,该方法基于细菌的游动反应,是非侵入性的,不需要进行任何遗传和/或机械准备,并且可以检测整个鞭毛束的行为。我们利用推理方法来测量天冬氨酸和α-甲基天冬氨酸的反应(以前用其他方法测量过),以及葡萄糖、亮氨酸和丝氨酸的反应。对葡萄糖这种吸引剂的反应被证明是双相的,并且与天冬氨酸一样完全适应。对丝氨酸这种吸引剂的反应也是双相的,但不完全适应,也就是说,响应函数的积分不为零(正)。亮氨酸这种抑制剂的反应的适应性也不完全,与丝氨酸相比,两个阶段的符号相反。对细菌种群的反应函数的多样性及其对背景浓度的依赖性进行了量化。