Exploring the Link Between Growth Regulation and Persister Formation

Many bacteria form persister cells that are transiently dormant and can withstand antimicrobials. Persisters necessitate long antimicrobial treatments and are a genetic reservoir that facilitates antimicrobial-resistance evolution. Using computational models Alicia studies how regulation of persister formation is intertwined with a bacterium’s growth and stress control circuits.

In E. coli, the alarmone ppGpp regulates anabolic vs catabolic gene expression and increases persister formation and stress tolerance at low growth rates. Thus, E. coli tunes it long-term fitness, given its current growth rate (short-term fitness). Using E. coli as a model organism Alicia studies how the ppGpp-mediated mechanism acts as a growth-rate dependent resource-allocation coordinator, balancing stress and growth tasks to maximise fitness. She studies how large fluctuations in ppGpp caused by nutrient shifts can initiate high Toxin and low Antitoxin levels in cells, shifting the cells from a growing to dormant state. Eventually, she will develop predictive models of antimicrobial effects given the growth, stress and persister-formation mechanisms.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 713669.