PT  - JOURNAL ARTICLE
AU  - Guillermo Rodrigo
AU  - Djordje Bajić
AU  - Ignacio Elola
AU  - Juan F. Poyatos
TI  - Dual autogenous control of the multiple antibiotic resistance phenotype in <em>Escherichia coli</em>
AID  - 10.1101/008169
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 008169
4099  - http://biorxiv.org/content/early/2014/08/19/008169.short
4100  - http://biorxiv.org/content/early/2014/08/19/008169.full
AB  - Bacteria can defend against diverse antibiotics by mounting a multiple antibiotic resistance (mar) phenotype. The resistance is linked to a chromosomal locus that encodes an activator and a repressor regulating their own expression. Here, we investigated how this dual autogenous control determines the dynamics of the response. We found that the regulatory architecture provides a mechanism to enable rapid induction, generate pulses of activation, and increase the range of sensing. The response is also graded and homogeneous across the population. Moreover, the interaction of a third regulator with the core module fine tunes the previous features, while limiting the cross-talk with metabolic signals. A minimal model accurately anticipates these properties, and emphasizes how specific attributes of the circuit components constrain the appearance of other potential behaviors associated to the regulatory design. Our results integrate both molecular and circuit-level characteristics to fully elucidate the dynamic emergence of the mar phenotype.