Quantifying Noise Correlations in the Multiple Antibiotic Resistance (Mar) Network

In dynamic and uncertain environments, bacterial populations can diversify and transiently express resistance genes in order to evade stressors. Stress response mechanisms often involve regulators controlling the expression of multiple downstream genes. In this work, we are interested in the multiple antibiotic resistance activator (MarA) controlling many downstream genes like those encoding the AcrAB-TolC efflux pump and the porin regulator gene micF. These genes require different levels of MarA to be induced. In our laboratory, we have recently shown that stochastic expression of MarA can provide antibiotic resistance at the single cell level. Our goal now is to determine how stochastic variability and noise in MarA propagates to its downstream genes. First, we constructed two double color plasmids expressing yellow and cyan fluorescent reporters for (i) marA and micF promoters and (ii) marA and acrAB promoters. Preliminary time-lapse movies showed that cyan and yellow fluorescence are correlated but dynamics between marA and micF differ from marA and acrAB reporters. Our approach will determine the magnitude of marA variability transmitted to these downstream genes in constant and varying environments. Overall, our goal is to studying dynamics in the Mar network to show how noise in one regulator and the diverse downstream genes it controls can leads diverse, transient antibiotic resistance levels within a population of bacteria.