Testing the optimality properties of a dual antibiotic treatment in a two-locus, two-allele model.
Testing the optimality properties of a dual antibiotic treatment in a two-locus, two-allele model.
复制标题
在双基因座、双等位基因模型中测试双抗生素治疗的最优特性。
DOI：
10.1098/rsif.2013.1035
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Peña-Miller R
中科院分区：
文献类型：
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作者：
Peña-Miller R
从数学上讲，这是不言自明的，复杂的，动态系统的最佳控制与许多相互作用的组件不能实现与“非响应”的控制策略，是恒定的。虽然有明显的例外，但这通常是我们设计抗菌药物治疗的方式，当我们每天给予相同剂量和相同的抗生素组合时。在这里，我们使用一个频率和密度依赖的药物遗传学数学模型，该模型基于细菌如何抵抗抗生素的标准，两个位点，两个等位基因表示，以探讨最佳抗生素治疗是否可能实际上是恒定的问题。该模型描述了在两种药物环境中竞争单一限制性资源的细菌大肠杆菌的不同亚群的生态和进化动力学。我们使用在vitroevolutionary实验来校准和测试模型，并表明抗生素环境可以支持动态变化和异质性的人口结构。然后，我们从理论和经验上证明，最好的治疗策略应该适应时间和恒定的策略不是最佳的。
Mathematically speaking, it is self-evident that the optimal control of complex, dynamical systems with many interacting components cannot be achieved with ‘non-responsive’ control strategies that are constant through time. Although there are notable exceptions, this is usually how we design treatments with antimicrobial drugs when we give the same dose and the same antibiotic combination each day. Here, we use a frequency- and density-dependent pharmacogenetics mathematical model based on a standard, two-locus, two-allele representation of how bacteria resist antibiotics to probe the question of whether optimal antibiotic treatments might, in fact, be constant through time. The model describes the ecological and evolutionary dynamics of different sub-populations of the bacteriumEscherichia colithat compete for a single limiting resource in a two-drug environment. We usein vitroevolutionary experiments to calibrate and test the model and show that antibiotic environments can support dynamically changing and heterogeneous population structures. We then demonstrate, theoretically and empirically, that the best treatment strategies should adapt through time and constant strategies are not optimal.