Mechanistic studies of life’s lower metabolic limits have been limited due to a paucity of tractable experimental systems. Here, we show that redox-cycling of phenazine-1-carboxamide (PCN) by Pseudomonas aeruginosa supports cellular maintenance in the absence of growth with a low mass-specific metabolic rate of 8.7 × 10⁻⁴ W (g C)⁻¹ at 25°C. Leveraging a high-throughput electrochemical culturing device, we find that non-growing cells cycling PCN tolerate conventional antibiotics but are susceptible to those that target membrane components. Under these conditions, cells conserve energy via a noncanonical, facilitated fermentation that is dependent on acetate kinase and NADH dehydrogenases. Across PCN concentrations that limit cell survival, the cell-specific metabolic rate is constant, indicating the cells are operating near their bioenergetic limit. This quantitative platform opens the door to further mechanistic investigations of maintenance, a physiological state that underpins microbial survival in nature and disease.

中文翻译：

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使用高通量电化学的低功率细菌维持状态的机理研究


由于缺乏易于处理的实验系统，对生命下代谢极限的机制研究受到限制。在这里，我们表明铜绿假单胞菌对奋静-1-甲酰胺 （PCN） 的氧化还原循环支持在没有生长的情况下进行细胞维持，在 25°C 下具有 8.7 × 10-4 W （g C）^-1 的低质量特异性代谢率。 利用高通量电化学培养装置，我们发现循环 PCN 的非生长细胞耐受常规抗生素，但对靶向膜成分的抗生素敏感。在这些条件下，细胞通过依赖于乙酸激酶和 NADH 脱氢酶的非经典、促进发酵来保存能量。在限制细胞存活的 PCN 浓度中，细胞特异性代谢率是恒定的，表明细胞在其生物能量极限附近运行。这个定量平台为进一步的维护机制研究打开了大门，维护是支撑微生物在自然界和疾病中生存的生理状态。