Stochastic simulations of the tetracycline operon

Simulations generate a timeline of biomolecular events that confer resistance to bacteria against tetracycline. We monitor the amounts of intracellular TetR2 and TetA proteins, the two important regulatory and resistance molecules, as a function of intrecellular tetracycline. We find that lack of one of the promoters of the tetracycline operon has no influence on the total behavior of this system inferring that this promoter is not essential for Escherichia coli. Sensitivity analysis with respect to the binding strength of tetracycline to repressor and of repressor to operators suggests that these two parameters play a predominant role in the behavior of the system. The results of the simulations agree well with experimental observations such as tight repression, fast gene expression, induction with tetracycline, and small intracellular TetR2 amounts.Computer simulations of the tetracycline operon afford augmented insight into the interplay between its molecular components. They provide useful explanations of how the components and their interactions have evolved to best serve bacteria carrying this operon. Therefore, simulations may assist in designing novel gene network architectures consisting of tetracycline operon components.Recent advances in our ability to mathematically investigate the dynamic complexity of biomolecular systems, have created inroads into these systems. Examples include natural systems, such as the lactose [1,2] and tryptophan [3] operon, and synthetic systems such as the oscillator [4,5], logic AND gates [6] and toggle switch [7]. In the present paper, we examine the dynamic behavior of the tetracycline (tet) operon. Although some studies have examined the interactions of different parts of the tet operon [8-10], to our knowledge there is no mathematical model that describes all the biomolecular interactions of this intriguing system. The tet operon is found naturally in bacteria where it confers resistance to antibiotic tetracycline (Tc).Tc