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Dual autogenous control of the multiple antibiotic resistance phenotype in Escherichia coli

Guillermo Rodrigo, Djordje Bajić, Ignacio Elola, Juan F. Poyatos
doi: https://doi.org/10.1101/008169
Guillermo Rodrigo
1Institute of Systems and Synthetic Biology, CNRS-UEVE, 91030 Évry, France
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Djordje Bajić
2Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain
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Ignacio Elola
2Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain
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Juan F. Poyatos
2Centro Nacional de Biotecnología, CSIC, 28049 Madrid, Spain
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  • For correspondence: jpoyatos@cnb.csic.es
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 19, 2014.
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Dual autogenous control of the multiple antibiotic resistance phenotype in Escherichia coli
Guillermo Rodrigo, Djordje Bajić, Ignacio Elola, Juan F. Poyatos
bioRxiv 008169; doi: https://doi.org/10.1101/008169
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Dual autogenous control of the multiple antibiotic resistance phenotype in Escherichia coli
Guillermo Rodrigo, Djordje Bajić, Ignacio Elola, Juan F. Poyatos
bioRxiv 008169; doi: https://doi.org/10.1101/008169

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