Dynamical determinants of drug-inducible gene expression in a single bacterium

¹ University of Chicago
² U of chicago
³ U of Chicago

^* To whom correspondence should be addressed. E-mail: cluzel{at}uchicago.edu.

Submitted on August 25, 2005
Revised on October 14, 2005
Accepted on 22 December 2005

	Abstract

A primitive example of adaptation in gene expression is the balance between the rate of synthesis and degradation of cellular RNA, which allows rapid responses to environmental signals (1). Here, we investigate how multi-drug efflux pump systems mediate the dynamics of a simple drug inducible system in response to a steady level of inducer. Using Fluorescence Correlation Spectroscopy (FCS), we measured in real-time within a single bacterium the transcription activity at the RNA level of the acrAB-TolC multi-drug efflux pump system. When cells are exposed to constant level of anhydrous tetracycline inducer and are adsorbed onto a poly-l-lysine coated surface, we found that the acrAB-TolC promoter is steadily active. We also monitored the activity of the tet promoter to characterize the effect of this efflux system on the dynamics of drug-inducible transcription. We found that the transcriptional response of the tet promoter to a steady level of aTc rises and then falls back to its pre-induction level. The rate of RNA degradation was constant throughout the transcriptional pulse, indicating that the modulation of intracellular inducer concentration alone can produce this pulsating response. Single-cell experiments together with numerical simulations suggest that such pulsating response in drug-inducible genetic systems is a property emerging from the dependence of drug-inducible transcription on multi-drug efflux systems.

Key Words: cellular dynamics, fcs, multi-drug efflux, rna decay, single cell, transcriptional network

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