Metabolic robustness to growth temperature of cold adapted bacterium

Microbial communities experience continuous environmental changes, among which temperature fluctuations are arguably the most impacting. This is particularly important considering the ongoing global warming but also simply in the context of seasonal variability of sea-surface temperature. Understanding how microorganisms react at the cellular level will improve our modelling and prediction of possible adaptations of microbial communities to a changing environment. In this work we asked which are the molecular mechanisms through which metabolic homeostasis is maintained in a cold-adapted bacterium during growth at temperatures that differ widely (0 and 15C). We have quantified its intracellular and extracellular metabolomes together with changes occurring at the transcriptomic level in the same growth conditions. This information was then used to contextualize a genome-scale metabolic reconstruction and to provide a systemic understanding of cellular adaptation to growth in a wide range of temperatures. Our findings indicate a strong metabolic robustness at the level of the main central metabolites, counteracted by a relatively deep transcriptomic reprogramming that includes changes in gene expression of hundreds of metabolic genes. We interpret this as a transcriptomic buffering of cellular metabolism, able to produce strikingly similar metabolic phenotypes despite the wide temperature gap. Moreover, we show that metabolic adaptation seems to be mostly played at the level of few key intermediates (e.g. phosphoenolpyruvate) and in the cross-talk between the main central metabolic pathways. Overall, our findings reveal a complex interplay at gene expression/resilience of core metabolism, also promoting the leveraging of state-of-the-art multi-disciplinary approaches to fully comprehend the molecular adaptation that occurs at different temperatures in bacteria.微生物群落持续面临各类环境变化，其中温度波动堪称影响最为深远的因素。这一论断尤为关键，不仅鉴于当前持续的全球变暖趋势，也契合海面温度季节性波动的现实背景。解析微生物在细胞层面的响应机制，可优化我们的建模与预测流程，进而更精准地预判微生物群落对环境变化的潜在适应策略。本研究旨在探究：一株嗜冷细菌在温差悬殊（0℃与15℃）的环境中生长时，维持代谢稳态的分子机制究竟为何。我们针对该菌株在相同培养条件下的细胞内外代谢组，以及转录组层面的表达变化进行了定量分析。依托上述分析结果，我们对基因组规模代谢重建模型进行了场景化适配，并系统阐释了该菌株在宽温度区间内生长时的细胞适应机制。研究结果表明，核心中央代谢物层面具备极强的代谢鲁棒性，而这一特性的维持依赖于涵盖数百个代谢相关基因表达变化的深度转录组重编程过程。我们将这一现象解读为细胞代谢的转录组缓冲机制：即便温度跨度极大，该机制仍能催生高度相似的代谢表型。此外，我们发现代谢适应主要通过少数关键中间代谢物（如磷酸烯醇式丙酮酸）以及核心中央代谢通路间的串扰来实现。总体而言，本研究揭示了核心代谢的基因表达与鲁棒性之间存在复杂的相互作用，同时也倡导借助前沿多学科研究方法，方能全面解析细菌在不同温度条件下的分子适应机制。