Dynamical properties of gene regulatory networks are tuned to ensure bacterial survival. In mycobacteria, the MprAB-σ^E network responds to the presence of stressors, such as surfactants that cause surface stress. Positive feedback loops in this network were previously predicted to cause hysteresis, i.e., different responses to identical stressor levels for prestressed and unstressed cells. Here, we show that hysteresis does not occur in nonpathogenic Mycobacterium smegmatis but does occur in Mycobacterium tuberculosis. However, the observed rapid temporal response in M. tuberculosis is inconsistent with the model predictions. To reconcile these observations, we implement a recently proposed mechanism for stress sensing, namely, the release of MprB from the inhibitory complex with the chaperone DnaK upon the stress exposure. Using modeling and parameter fitting, we demonstrate that this mechanism can accurately describe the experimental observations. Furthermore, we predict perturbations in DnaK expression that can strongly affect dynamical properties. Experiments with these perturbations agree with model predictions, confirming the role of DnaK in fast and sustained response.

中文翻译：

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结核分枝杆菌中伴侣介导的压力感应能够实现快速激活和持续反应

调整基因调控网络的动态特性以确保细菌存活。在分枝杆菌中，MprAB-σ ^E网络对压力源的存在做出反应，例如引起表面应力的表面活性剂。先前预测该网络中的正反馈回路会导致滞后，即对预应力和非应力细胞对相同压力源水平的不同反应。在这里，我们表明滞后不会发生在非致病性耻垢分枝杆菌中，但确实发生在结核分枝杆菌中。然而，在结核分枝杆菌中观察到的快速时间反应与模型预测不一致。为了调和这些观察结果，我们实施了最近提出的压力感应机制，即在压力暴露时 MprB 从抑制性复合物与伴侣 DnaK 中释放。使用建模和参数拟合，我们证明了这种机制可以准确地描述实验观察。此外，我们预测 DnaK 表达的扰动会强烈影响动力学特性。这些扰动的实验与模型预测一致，证实了 DnaK 在快速和持续响应中的作用。