High growth rates can promote persister cell formation in <i>Pseudomonas aeruginosa</i>

Bacterial persister cells are characterized by arrested growth and survival in normally lethal antibiotic concentrations. Observations of persistence peaking in the stationary phase suggest that its function may be associated with slow growth, potentially acting as a 'bet-hedging' strategy under stress. However, fundamental questions remain about the adaptive function of persistence and how it evolves, as no genetic mechanism has been identified and only a small fraction of the population (≤1%) is in a persistent state at any time. To test whether slow growth conditions promote persistence, we manipulated population growth rate by initiating cultures with different densities of inoculum and compared persistence across growth curve phases. We conducted these experiments in a well-studied Escherichia coli strain and the pathogen Pseudomonas aeruginosa, in which persistence is known to present a challenge to lung infection treatments. While E. coli exhibited persistence predominantly during the stationary phase as previously reported, peaks in persistence were detected during the exponential phase and even the lag phase in P. aeruginosa cultures inoculated with low-density inoculum. Further assays identified factors associated with the internal cell state, which require further investigation but suggest that patterns of persistence in E. coli may not be representative of other species and that persistence may also be linked with population cell division history and metabolic state.