Knapp Benjamin D, Willis Lisa, Gonzalez Carlos, Vashistha Harsh, Touma Joanna Jammal, Tikhonov Mikhail, Ram Jeffrey, Salman Hanna, Elias Josh E, Huang Kerwyn Casey
Biophysics Program, Stanford University, Stanford, CA 94305, USA.
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
bioRxiv. 2023 Aug 30:2023.07.22.550177. doi: 10.1101/2023.07.22.550177.
Temperature is one of the key determinants of microbial behavior and survival, whose impact is typically studied under heat- or cold-shock conditions that elicit specific regulation to combat lethal stress. At intermediate temperatures, cellular growth rate varies according to the Arrhenius law of thermodynamics without stress responses, a behavior whose origins have not yet been elucidated. Using single-cell microscopy during temperature perturbations, we show that bacteria exhibit a highly conserved, gradual response to temperature upshifts with a time scale of ~1.5 doublings at the higher temperature, regardless of initial/final temperature or nutrient source. We find that this behavior is coupled to a temperature memory, which we rule out as being neither transcriptional, translational, nor membrane dependent. Instead, we demonstrate that an autocatalytic enzyme network incorporating temperature-sensitive Michaelis-Menten kinetics recapitulates all temperature-shift dynamics through metabolome rearrangement, which encodes a temperature memory and successfully predicts alterations in the upshift response observed under simple-sugar, low-nutrient conditions, and in fungi. This model also provides a mechanistic framework for both Arrhenius-dependent growth and the classical Monod Equation through temperature-dependent metabolite flux.
温度是微生物行为和生存的关键决定因素之一,其影响通常在热休克或冷休克条件下进行研究,这些条件会引发特定的调节以对抗致命压力。在中等温度下,细胞生长速率根据热力学的阿伦尼乌斯定律变化,且无应激反应,这种行为的起源尚未阐明。在温度扰动期间使用单细胞显微镜,我们发现细菌对温度升高表现出高度保守的渐进反应,在较高温度下的时间尺度约为1.5代,无论初始/最终温度或营养源如何。我们发现这种行为与温度记忆相关联,我们排除了它既不是转录依赖、翻译依赖也不是膜依赖的可能性。相反,我们证明了一个包含温度敏感米氏动力学的自催化酶网络通过代谢组重排概括了所有温度变化动态,该网络编码温度记忆,并成功预测了在单糖、低营养条件下以及在真菌中观察到的升温反应变化。该模型还通过温度依赖性代谢物通量为阿伦尼乌斯依赖生长和经典的莫诺德方程提供了一个机制框架。