Optogenetic Control of Antibiotic Resistance to Understand Impact of Activation Dynamics on Bacterial Survival

The spread of antibiotic resistance is a major threat to human health. The single-cell dynamics surrounding the activation of resistance genes are often unknown, and insight into these dynamics can lead to improved strategies for mediating resistant infections. Specifically, the impact of resistance activation timing relative to antibiotic exposure on mixed-resistance community survival may provide insight on how to best time antibiotic doses and concentrations to prevent acquisition and proliferation of resistance.

We use an optogenetic Cre recombinase control system to regulate the activation of resistance genes over time, allowing for spatiotemporal control of resistance. Here, we characterize how the timing of resistance acquisition in a subset of the population affects growth rate and final percentage of resistant cells in the population. We present work towards understanding the impact of the resistance mechanism, initial resistant fraction, and resistance activation timing on bacterial survival.