Plenary Talk 21st International Conference on Biological Inorganic Chemistry 2025

Phenazines Facilitate an Extremely Low Power Maintenance Metabolism on Life’s Metabolic Edge (124975)

Dianne K Newman 1
  1. Caltech, Pasadena, CA, United States

Mechanistic studies of life’s lower metabolic limits have been limited due to a paucity of tractable experimental systems. In this talk, I will describe how we can investigate the physiology of maintenance through studying anaerobic phenazine cycling by bacteria.  Phenazines are a class of redox-active metabolites produced by diverse organisms.  Using Pseudomonas aeruginosa as a model phenazine-producer, we have shown that anaerobic phenazine cycling supports cellular maintenance in the absence of growth with a very low mass-specific metabolic rate (amongst the lowest ever measured for any organism). In this state, non-growing cells tolerate conventional antibiotics, motivating the identification of cellular machinery that underpin maintenance metabolism as a first step towards identifying better drug targets.  I will show how a quantitative, high-throughput electrochemical platform can be leveraged to identify this machinery, providing a specific example of a bioenergetic pathway that permits energy conservation under these conditions. This platform opens the door to further mechanistic investigations of maintenance, a physiological state that underpins microbial survival in nature and disease.