A Network Biology Approach to Denitrification in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a metabolically flexible member of the Gammaproteobacteria. Under anaerobic conditions and the presence of nitrate, P. aeruginosa can perform (complete) denitrification, a respiratory process of dissimilatory nitrate reduction to nitrogen gas via nitrite (NO2), nitric oxide (NO) and nitrous oxide (N2O). This study focuses on understanding the influence of environmental conditions on bacterial denitrification performance, using a mathematical model of a metabolic network in P. aeruginosa. To our knowledge, this is the first mathematical model of denitrification for this bacterium. Analysis of the long-term behavior of the network under changing concentration levels of oxygen (O2), nitrate (NO3), and phosphate (PO4) suggests that PO4 concentration strongly affects denitrification performance. The model provides three predictions on denitrification activity of P. aeruginosa under various environmental conditions, and these predictions are either experimentally validated or supported by pertinent biological literature. One motivation for this study is to capture the effect of PO4 on a denitrification metabolic network of P. aeruginosa in order to shed light on mechanisms for greenhouse gas N2O accumulation during seasonal oxygen depletion in aquatic environments such as Lake Erie (Laurentian Great Lakes, USA). Simulating the microbial production of greenhouse gases in anaerobic aquatic systems such as Lake Erie allows a deeper understanding of the contributing environmental effects that will inform studies on, and remediation strategies for, other hypoxic sites worldwide.铜绿假单胞菌（Pseudomonas aeruginosa）是一类代谢灵活性极强的γ-变形菌纲（Gammaproteobacteria）成员。在厌氧条件且存在硝酸盐的环境中，该菌可进行完整反硝化（denitrification）作用：这是一类通过亚硝酸盐（NO2）、一氧化氮（NO）与一氧化二氮（N2O）作为中间代谢物，将硝酸盐异化还原为氮气的呼吸代谢过程。本研究旨在解析环境条件对细菌反硝化性能的影响，采用的研究工具为铜绿假单胞菌代谢网络的数学模型。据我们所知，这是针对该菌种反硝化作用的首个数学模型。通过分析该代谢网络在氧（O2）、硝酸盐（NO3）与磷酸盐（PO4）浓度动态变化下的长期行为，结果表明磷酸盐浓度对反硝化性能具有显著调控作用。该模型针对铜绿假单胞菌在多种环境条件下的反硝化活性提出了三项预测，且这些预测要么已通过实验验证，要么得到相关生物学文献的佐证。本研究的核心动机之一，是通过刻画磷酸盐对铜绿假单胞菌反硝化代谢网络的影响机制，以阐明美国劳伦琴五大湖中的伊利湖等水生环境在季节性缺氧时温室气体N2O累积的内在原理。通过模拟伊利湖这类厌氧水生系统中微生物的温室气体生成过程，可更深入地解析相关驱动环境因子，这将为全球其他缺氧生境的相关研究与修复策略提供科学参考。