ARTICLE: Cellular energy budgets and antimicrobial resistance

Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression
Ryan Kerr, Sara Jabbari, Jessica MA Blair, Iain G Johnston
Journal of the Royal Society Interface 19 20210771 (2021)

Antimicrobial resistance or AMR is a major global health issue, with disease-causing organisms like bacteria acquiring resistance to the drugs we use to kill them. One way that bacteria acquire this resistance is through so-called efflux pumps -- cellular machinery that removes chemicals like drugs from inside the bacterium. Bacteria produce these pumps when faced with drug treatments, but not all cells produce the same amount or at the same time. Understanding this variability could help the theory behind future treatments.

After finding that the available "energy budget" influences the behaviour of cellular programs, we asked whether energy variability could be a cause of these differences. Using lots of diverse experimental observations, we built a theoretical model of the signals that tell a bacterium to produce efflux pumps in response to sensing a drug, with a new and simple way of accounting for how energy affects these signals. We then simulated this model in a computer to see how model cells with different amounts of available energy (as we see in real bacterial populations) behaved.

We found that differences in cellular energy budgets can have a profound effect on when, and how much, efflux machinery is produced. This variability builds on the natural randomness of the system, leading to several interesting results: energy changes the dynamics of how signalling programs work in the cell, alters timescales, and affects the "priming" of a population of cells to anticipate future stress. The approach we developed is quite general and can be used to explore energy influence on any other cell programs and signals too.

Including ATP, an important cellular energy currency, in models of how bacteria express efflux machinery helps us understand how cell-to-cell differences in energy budget may influence AMR.