A theoretical analysis of the prodrug delivery system for treating antibiotic-resistant bacteria

IEEE/ACM Transactions on Computational Biology and Bioinformatics
James T MurphyMarc Devocelle

Abstract

Simulations were carried out to analyze a promising new antimicrobial treatment strategy for targeting antibiotic-resistant bacteria called the β-lactamase-dependent prodrug delivery system. In this system, the antibacterial drugs are delivered as inactive precursors that only become activated after contact with an enzyme characteristic of many species of antibiotic-resistant bacteria (β-lactamase enzyme). The addition of an activation step contributes an extra layer of complexity to the system that can lead to unexpected emergent behavior. In order to optimize for treatment success and minimize the risk of resistance development, there must be a clear understanding of the system dynamics taking place and how they impact on the overall response. It makes sense to use a systems biology approach to analyze this method because it can facilitate a better understanding of the complex emergent dynamics arising from diverse interactions in populations. This paper contains an initial theoretical examination of the dynamics of this system of activation and an assessment of its therapeutic potential from a theoretical standpoint using an agent-based modeling approach. It also contains a case study comparison with real-world results from ...Continue Reading

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