Department of Chemical and Biological Engineering, Center for Biofilm Engineering, Montana State University, Bozeman, MT, 59717, USA.
Department of Microbiology and Immunology, Montana State University, Bozeman, MT, 59717, USA.
Sci Rep. 2021 Jan 14;11(1):1457. doi: 10.1038/s41598-020-80522-8.
Pseudomonas aeruginosa is a globally-distributed bacterium often found in medical infections. The opportunistic pathogen uses a different, carbon catabolite repression (CCR) strategy than many, model microorganisms. It does not utilize a classic diauxie phenotype, nor does it follow common systems biology assumptions including preferential consumption of glucose with an 'overflow' metabolism. Despite these contradictions, P. aeruginosa is competitive in many, disparate environments underscoring knowledge gaps in microbial ecology and systems biology. Physiological, omics, and in silico analyses were used to quantify the P. aeruginosa CCR strategy known as 'reverse diauxie'. An ecological basis of reverse diauxie was identified using a genome-scale, metabolic model interrogated with in vitro omics data. Reverse diauxie preference for lower energy, nonfermentable carbon sources, such as acetate or succinate over glucose, was predicted using a multidimensional strategy which minimized resource investment into central metabolism while completely oxidizing substrates. Application of a common, in silico optimization criterion, which maximizes growth rate, did not predict the reverse diauxie phenotypes. This study quantifies P. aeruginosa metabolic strategies foundational to its wide distribution and virulence including its potentially, mutualistic interactions with microorganisms found commonly in the environment and in medical infections.
铜绿假单胞菌是一种分布广泛的细菌，通常存在于医学感染中。这种机会性病原体使用一种不同于许多模型微生物的碳分解代谢物阻遏（CCR）策略。它不利用经典的双重发酵表型，也不遵循包括优先消耗葡萄糖和“溢出”代谢等常见系统生物学假设。尽管存在这些矛盾，但铜绿假单胞菌在许多不同的环境中具有竞争力，这突显了微生物生态学和系统生物学中的知识空白。本研究使用生理、组学和计算机模拟分析来量化铜绿假单胞菌的 CCR 策略，即“反向双重发酵”。使用经过体外组学数据检验的基因组规模代谢模型，确定了反向双重发酵的生态基础。通过一种多维策略预测了反向双重发酵对低能量、不可发酵碳源（如乙酸盐或琥珀酸盐）的偏好，而不是葡萄糖，该策略最大限度地减少了对中心代谢的资源投入，同时完全氧化了底物。应用一种常见的、计算机模拟优化标准，该标准最大限度地提高了生长速率，并没有预测到反向双重发酵表型。这项研究量化了铜绿假单胞菌的代谢策略，这些策略是其广泛分布和毒力的基础，包括其与环境中和医学感染中常见的微生物的潜在共生相互作用。
