The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake inStreptococcus mutans
The Pta-AckA Pathway Regulates LrgAB-Mediated Pyruvate Uptake inStreptococcus mutans
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DOI：
10.3390/microorganisms8060846
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发表时间：
2020-06-01
期刊：
影响因子：
4.5
通讯作者：
Rice, Kelly C.
中科院分区：
文献类型：
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作者：
Ahn, Sang-Joon;Desai, Shailja;Rice, Kelly C.
丙酮酸形成碳代谢的中心节点，并在饥饿期间作为替代碳源促进生长。我们最近揭示了LrgAB在变形链球菌中作为一个固定相丙酮酸摄取系统的功能，而变形链球菌是人类龋病的主要病因，但其潜在的调控机制仍不清楚。本研究旨在从代谢组学的角度进一步研究LrgAB的调节作用。我们利用了一系列的GFP定量、生长动力学和生化分析。我们发现LrgAB对于丙酮酸的摄取是至关重要的，尤其是在低糖胁迫下的生长过程中。负责乙酰-辅酶A转化为乙酸酯的PTA-Ack途径的失活，完全抑制了固定相rgAB的诱导和丙酮酸的摄取，并使细胞对外部丙酮酸信号不敏感。在厌氧条件下，负责丙酮酸转化为乙酰辅酶A的PFL失活，也影响了固定相丙酮酸的摄取。本研究探讨了通过LrgAB调节丙酮酸摄取的代谢成分，并强调了其作为代谢刺激物的潜力，有助于OFS的复苏和存活。营养应激时的突变细胞。
Pyruvate forms the central node of carbon metabolism and promotes growth as an alternative carbon source during starvation. We recently revealed that LrgAB functions as a stationary phase pyruvate uptake system inStreptococcus mutans,the primary causative agent of human dental caries, but its underlying regulatory mechanisms are still not clearly understood. This study was aimed at further characterizing the regulation of LrgAB from a metabolomic perspective. We utilized a series of GFP quantification, growth kinetics, and biochemical assays. We disclosed that LrgAB is critical for pyruvate uptake especially during growth under low-glucose stress. Inactivation of the Pta-Ack pathway, responsible for the conversion of acetyl-CoA to acetate, completely inhibits stationary phaselrgABinduction and pyruvate uptake, and renders cells insensitive to external pyruvate as a signal. Inactivation of Pfl, responsible for the conversion of pyruvate to acetyl-CoA under anaerobic conditions, also affected stationary phase pyruvate uptake. This study explores the metabolic components of pyruvate uptake regulation through LrgAB, and highlights its potential as a metabolic stimulator, contributing to the resuscitation and survival ofS. mutanscells during nutritional stress.