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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.

Rights:

• Creative Commons BY-NC-ND Attribution-NonCommercial-NoDerivs 4.0 International
  

Keyword: Phenazine

Date published: 2024-10-23

Publisher: Elsevier BV

Journal:

• Cell (ISSN: 00928674) vol. 187 issue. 24 p. 6882-6895

Funding:

• National Institute of Allergy and Infectious Diseases
• Japan Science and Technology Agency
• Japan Society for the Promotion of Science

Manuscript type: Author's version (Accepted manuscript)

MDR DOI: https://doi.org/10.48505/nims.5166

First published URL: https://doi.org/10.1016/j.cell.2024.09.042

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Updated at: 2025-10-23 08:30:36 +0900

Published on MDR: 2025-10-23 08:18:23 +0900