美国加州理工学院Dianne K. Newman等研究人员合作完成通过高通量电化学对低能耗细菌维持状态的机制研究。相关论文于2024年10月23日在线发表在《细胞》杂志上。
研究人员展示了铜绿假单胞菌通过对苯嗪-1-羧酰胺（PCN）的氧化还原循环支持细胞在无生长状态下的维持，其质量特异性代谢率在25°C下为8.7 × 10−4 W (g C)−1。利用高通量电化学培养设备，研究人员发现循环PCN的非生长细胞对传统抗生素具有耐受性，但对那些靶向膜成分的抗生素则易感。
在这些条件下，细胞通过一种非经典的、依赖于乙酸激酶和NADH脱氢酶的促进发酵方式来节能。在限制细胞存活的不同PCN浓度下，细胞特定代谢率保持恒定，表明细胞的生物能量极限接近。这一定量平台为进一步研究维持机制提供了可能，这是支撑微生物在自然界和疾病中生存的生理状态。
据了解，由于缺乏可操作的实验系统，生命的最低代谢极限的机制研究受到限制。
附：英文原文
Title: Mechanistic study of a low-power bacterial maintenance state using high-throughput electrochemistry
Author: John A. Ciemniecki, Chia-Lun Ho, Richard D. Horak, Akihiro Okamoto, Dianne K. Newman
Issue&Volume: 2024-10-23
Abstract: 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 × 104 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.
DOI: 10.1016/j.cell.2024.09.042
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01142-5