Contextual flexibility in Pseudomonas aeruginosa central carbon metabolism during growth in single carbon sources
Contextual flexibility in Pseudomonas aeruginosa central carbon metabolism during growth in single carbon sources
复制标题
单一碳源生长过程中铜绿假单胞菌中心碳代谢的环境灵活性
DOI：
10.1101/828012
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Dolan S
中科院分区：
文献类型：
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作者：
Dolan S
铜绿假单胞菌是一种机会性人类病原体，特别是引起囊性纤维化（CF）患者肺部感染。以往的研究表明，P.当机体适应CF气道环境时，呼吸道似乎朝向共同的代谢程序收敛。然而，在系统水平上，我们对这些转录变化如何影响代谢通量仍然只有有限的了解。为了解决这个问题，我们分析了转录组，蛋白质组和通量。在甘油或乙酸盐上的aerodysosagrown。选择这些碳源是因为它们是气道表面活性剂磷脂酰胆碱的主要分解产物，已知磷脂酰胆碱是P的主要碳源。CF气道中的通气孔。我们表明，通过中央代谢的碳通量是从根本上不同的每一个碳源。例如，新认识到的EDEMP循环在甘油生长期间提供NADPH方面发挥重要作用。相比之下，EDEMP循环在乙酸盐上生长期间减弱，相反，NADPH主要由异柠檬酸脱氢酶催化的反应提供。也许更重要的是，我们的蛋白质组学和转录组学分析揭示了在不同碳源上生长期间基因表达的全球重塑，对好氧反硝化，电子传递链结构和细胞的氧化还原经济产生了意想不到的影响。总的来说，这些数据突出了P的显著代谢可塑性。铜绿;重要性铜绿假单胞菌是一种机会性的人类病原体，以引起囊性纤维化患者的气道感染而闻名。虽然很明显P。尽管呼吸道细菌在代谢上很好地适应了CF肺中的生活，但目前对该生物体如何代谢气道中可用的营养素知之甚少。在这项工作中，我们使用基因表达和同位素示踪（“fluxomic”）分析的组合，以找出在两个CF相关的碳源，乙酸和甘油（来自肺表面活性物质的分解）生长过程中输入碳的确切位置。我们发现，碳是路由（“fluxed”）通过非常不同的途径在这些基板上的生长过程中，这是伴随着一个意想不到的重塑细胞的电子转移途径。有机会获得这一“蓝图”是重要的，因为代谢ofP。越来越多的人认识到空气微生物是开发急需的抗微生物剂的目标。
Pseudomonas aeruginosais an opportunistic human pathogen, particularly noted for causing infections in the lungs of people with cystic fibrosis (CF). Previous studies have shown that the gene expression profile ofP. aeruginosaappears to converge towards a common metabolic program as the organism adapts to the CF airway environment. However, at a systems level, we still have only a limited understanding of how these transcriptional changes impact on metabolic flux. To address this, we analysed the transcriptome, proteome and fluxome ofP. aeruginosagrown on glycerol or acetate. These carbon sources were chosen because they are the primary breakdown products of airway surfactant, phosphatidylcholine, which is known to be a major carbon source forP. aeruginosain the CF airways. We show that the flux of carbon through central metabolism is radically different on each carbon source. For example, the newly-recognised EDEMP cycle plays an important role in supplying NADPH during growth on glycerol. By contrast, the EDEMP cycle is attenuated during growth on acetate, and instead, NADPH is primarily supplied by the isocitrate dehydrogenase(s)-catalyzed reaction. Perhaps more importantly, our proteomic and transcriptomic analyses reveal a global remodelling of gene expression during growth on the different carbon sources, with unanticipated impacts on aerobic denitrification, electron transport chain architecture, and the redox economy of the cell. Collectively, these data highlight the remarkable metabolic plasticity ofP. aeruginosa; a plasticity which allows the organism to seamlessly segue between different carbon sources, maximising the energetic yield from each.ImportancePseudomonas aeruginosais an opportunistic human pathogen, well-known for causing infections in the airways of people with cystic fibrosis. Although it is clear thatP. aeruginosais metabolically well-adapted to life in the CF lung, little is currently known about how the organism metabolises the nutrients available in the airways. In this work, we use a combination of gene expression and isotope tracer (“fluxomic”) analyses to find out exactly where the input carbon goes during growth on two CF-relevant carbon sources, acetate and glycerol (derived from the breakdown of lung surfactant). We find that carbon is routed (“fluxed”) through very different pathways during growth on these substrates, and that this is accompanied by an unexpected remodelling of the cell’s electron transfer pathways. Having access to this “blueprint” is important because the metabolism ofP. aeruginosais increasingly being recognised as a target for the development of much-needed antimicrobial agents.