バクテリアの 「冬眠状態 」を示す新技術(New Technology Illustrates Bacterial “Hibernation States”)

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2024-10-23 カリフォルニア工科大学(Caltech)

新技術により、細菌が抗生物質に耐える「低代謝状態」を詳細に研究できるようになりました。従来、細菌が抗生物質に耐えるバイオフィルムの中心部で、成長せずに生き残る低代謝状態を研究することは困難でしたが、カリフォルニア工科大学と日本の国立材料研究所のチームが96チャンネルポテンショスタットを用いて、この状態の代謝を高精度で測定できるシステムを開発しました。この技術により、新たな薬剤標的の発見が期待されています。

<関連情報>

ハイスループット電気化学を用いた細菌の低電力維持状態のメカニズム研究 Mechanistic study of a low-power bacterial maintenance state using high-throughput electrochemistry

John A. Ciemniecki∙ Chia-Lun Ho∙ Richard D. Horak∙ Akihiro Okamoto∙ Dianne K. Newman
Cell  Published:October 23, 2024
DOI:https://doi.org/10.1016/j.cell.2024.09.042

Graphical abstract

バクテリアの 「冬眠状態 」を示す新技術(New Technology Illustrates Bacterial “Hibernation States”)

Highlights

•Anaerobic PCN cycling supports a low metabolic rate (∼103 ATP s-1 cell-1 at 25°C)
•During PCN cycling, single cells maintain metabolic activity but do not grow
•A high-throughput electrochemical platform enables mechanistic studies of maintenance
•Disrupting membrane integrity or bioenergetic components impairs survival in this state

Summary

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.

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