Don't Let History Repeat Itself: Optimal Multidrug Quorum Quenching of Pathogens Network

Recent advances in synthetic biology have dramatically expanded our ability to control biological processes at the cellular level. Particularly, a large body of recent work focuses on human pathogen treatment targeting increased antibiotic resistance. To this end, a new strategy has been proposed to disrupt the pathogen communication network (i.e., quorum sensing (QS)) such that the pathogens cannot coordinate the release of virulence factors. In this paper, we propose a new molecular model that captures the effects of QSIs on the QS network of P. aeruginosa and formulate a constrained optimization problem to find the optimal combination of QSIs while accounting for the selective pressure of developing drug resistance. Our optimization results show significant reduction of selective pressure on pathogens, while preserving the efficacy of the multidrug quorum quenching therapy.

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