Autonomous and Adaptive Control of Populations of Bacteria Through Environment Regulation

摘要

The proliferation of antibiotic-resistant bacteria poses a significant threat to humans health and welfare. To reduce the bacterial pathogenesis and growth, we propose an autonomous biological controller that can adaptively generate quorum sensing inhibitors and control the iron availability in the environment. As the main theoretical contribution, we provide a detailed analysis of our proposed controller that includes model calibration, system response, and inhibitor effectiveness. We also formulate a constrained optimization problem to choose the values of the biological parameters of the proposed controller under given environment constraints. Finally, we validate our results via detailed population-level simulations and demonstrate that bacteria virulence can be significantly reduced without developing drug resistance or inducing selective pressure among bacteria wild type and mutants. This work represents a first step towards a paradigm change in reducing bacterial pathogenesis via controlling the dynamics of the cell-cell communication through environment regulation.