揭示应激源三元组合中的新出现的相互作用。
Uncovering emergent interactions in three-way combinations of stressors.
作者信息
Beppler Casey, Tekin Elif, Mao Zhiyuan, White Cynthia, McDiarmid Cassandra, Vargas Emily, Miller Jeffrey H, Savage Van M, Yeh Pamela J
机构信息
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics, The Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
出版信息
J R Soc Interface. 2016 Dec;13(125). doi: 10.1098/rsif.2016.0800.
Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two component) interactions have been lacking. Here, we conduct experiments using 20 three-drug combinations and their effects on the bacterial growth of Escherichia coli We report our measurements of growth rates in single, pairwise and triple-drug combinations. To uncover emergent interactions, we derive a simple framework to calculate expectations for three-way interactions based on the measured impact of each individual stressor and of each pairwise interaction. Using our framework, we find that (i) emergent antagonisms are more common than emergent synergies and (ii) emergent antagonisms are more common and emergent synergies are more rare than would be inferred from measures of net effects that do not disentangle pairwise interactions from three-way interactions.
要预测各种生物系统的动态结果，需要了解多种应激源如何相互作用，这些生物系统包括采用联合药物疗法对抗和治疗的耐药病原体，以及受到环境毒物或干扰影响的生态系统。然而，对高阶（超过两个组分）相互作用的广泛研究一直缺乏。在这里，我们使用20种三联药物组合进行实验，并研究它们对大肠杆菌细菌生长的影响。我们报告了在单一、两两组合和三联药物组合情况下对生长速率的测量结果。为了揭示新出现的相互作用，我们推导了一个简单的框架，基于每个单独应激源和每个两两相互作用的测量影响来计算三向相互作用的预期值。使用我们的框架，我们发现：（i）新出现的拮抗作用比新出现的协同作用更常见；（ii）与从未将两两相互作用与三向相互作用区分开的净效应测量中推断的情况相比，新出现的拮抗作用更常见，新出现的协同作用更罕见。
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