How master regulators coordinate antibiotic resistance without sacrificing downstream specialization

Invited Speaker : Nicholas Rossi (University of Vermont).

How master regulators coordinate antibiotic resistance without sacrificing downstream specialization

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. In this talk, I will focus 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. Employing tools from information theory and statistical mechanics, I analyze single-cell experiments and build models to show that each downstream gene has distinct activation, noise, and information transmission properties. Critically, these results demonstrate that understanding biological context is essential ; finding 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. By combining theory, modeling and experimentation, these results demonstrate how a single regulatory protein can maintain specificity while orchestrating the response of many downstream genes.

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