Customized Regulation of Diverse Stress Response Genes by the Multiple Antibiotic Resistance Activator MarA

Abstract

Stress response networks frequently have a single upstream regulator that controls many downstream genes. However, the downstream targets are often diverse, therefore it remains unclear how their expression is specialized when under the command of a common regulator. To address this, we focused on a stress response network where the multiple antibiotic resistance activator MarA from Escherichia coli regulates diverse targets ranging from small RNAs to efflux pumps. Using single-cell experiments and computational modeling, we showed that each downstream gene studied has distinct activation, noise, and information transmission properties. Critically, our results demonstrate that understanding biological context is essential; we found examples where strong activation only occurs outside physiologically relevant ranges of MarA and others where noise is high at wild type MarA levels and decreases as MarA reaches its physiological limit. These results demonstrate how a single regulatory protein can maintain specificity while orchestrating the response of many downstream genes.