Abstract

Historically, the study of bacterial physiology and regulation has focused on populations of cells growing exponentially, in part because the cellular system can be assumed to be at steady state (to a first approximation) under these conditions. In exponential growth, bacterial gene expression is controlled predominantly at the level of transcription initiation and is regulated to optimise growth rate given the available nutrients. However, in many environmental contexts, including infections, bacterial populations are not in exponential, steady state growth and instead are subjected to growth-arresting nutrient depletion or stress. Much less is known about regulatory capacities and mechanisms under these conditions. We have focused on measuring biosynthetic activities and regulatory mechanisms in Pseudomonas aeruginosa starved for carbon or nitrogen sources. We find that viability, new protein synthesis, and flagellar motility are maintained over many days of total starvation, and we have begun to characterise the regulatory networks controlling these activities. A major motivation for investigating growth arrest activities and regulation is the growing understanding that the growth-arrested bacteria commonly found in chronic infection contexts are tolerant of the most commonly used antibiotics. I will finish by describing our efforts to leverage our investigations into growth arrest to identify novel targets for anti-bacterial therapeutics.