From transcriptional landscapes to the identification of biomarkers for robustness.
From transcriptional landscapes to the identification of biomarkers for robustness.
复制标题
DOI：
10.1186/1475-2859-10-s1-s9
复制
发表时间：
2011-08-30
影响因子：
6.4
通讯作者：
den Besten H
中科院分区：
文献类型：
--
作者：
Abee T;Wels M;de Been M;den Besten H
微生物适应不断变化的环境和获得细胞稳健性的能力，挑战了对其历史依赖行为的预测。使用我们的模式生物蜡样芽孢杆菌，一种臭名昭著的革兰氏阳性食物腐败和致病孢子形成细菌，将描述一种策略，允许识别生物标志物的鲁棒性。首先将概述其双组分系统，通常包括跨膜传感器组氨酸激酶及其同源反应调节器，允许对环境波动做出快速而稳健的反应。强调了多传感器杂交激酶RsbK和pp2c型磷酸酶RsbY系统在激活一般应激因子σB中的作用。通过对蜡样芽孢杆菌在热、酸、盐和氧化等温和胁迫条件下的转录图谱进行比较分析，发现在大多数条件下均能诱导出σB调控基因。从转录组数据中获得的信息随后被应用于识别和选择细胞生物标志物mRNA、蛋白质和/或活性水平的框架中，用于轻度应激诱导的微生物对致死应激的稳健性。将非应激和适应轻度应激的细胞暴露于随后的致死应激条件下（热、酸和氧化应激），可以使用板计数法对轻度应激预处理提供的稳健性优势进行量化。所选择的候选生物标志物、σB蛋白、过氧化氢酶活性和某些蛋白酶转录物在轻度胁迫下的诱导水平与轻度胁迫诱导的致死性热、氧化和酸胁迫增强的鲁棒性显著相关，因此适合预测这些适应性状。与适应行为定量相关的细胞生物标志物将有助于我们预测适应行为对细胞鲁棒性的影响，并将允许控制和/或利用这些适应特征。外推到其他物种和属的讨论，如途径对微生物适应性和鲁棒性的机制为基础的设计。
The ability of microorganisms to adapt to changing environments and gain cell robustness, challenges the prediction of their history-dependent behaviour. Using our model organism Bacillus cereus, a notorious Gram-positive food spoilage and pathogenic spore-forming bacterium, a strategy will be described that allows for identification of biomarkers for robustness. First an overview will be presented of its two-component systems that generally include a transmembrane sensor histidine kinase and its cognate response regulator, allowing rapid and robust responses to fluctuations in the environment. The role of the multisensor hybrid kinase RsbK and the PP2C-type phosphatase RsbY system in activation of the general stress sigma factor σB is highlighted. An extensive comparative analysis of transcriptional landscapes derived from B. cereus exposed to mild stress conditions such as heat, acid, salt and oxidative stress, revealed that, amongst others σB regulated genes were induced in most conditions tested. The information derived from the transcriptome data was subsequently implemented in a framework for identifying and selecting cellular biomarkers at their mRNA, protein and/or activity level, for mild stressinduced microbial robustness towards lethal stresses. Exposure of unstressed and mild stress-adapted cells to subsequent lethal stress conditions (heat, acid and oxidative stress) allowed for quantification of the robustness advantage provided by mild stress pretreatment using the plate-count method. The induction levels of the selected candidate-biomarkers, σB protein, catalase activity and transcripts of certain proteases upon mild stress treatment, were significantly correlated to mild stress-induced enhanced robustness towards lethal thermal, oxidative and acid stresses, and were therefore suitable to predict these adaptive traits. Cellular biomarkers that are quantitatively correlated to adaptive behavior will facilitate our ability to predict the impact of adaptive behavior on cell robustness and will allow to control and/or exploit these adaptive traits. Extrapolation to other species and genera is discussed such as avenues towards mechanism-based design of microbial fitness and robustness.