Aaron Hinz, André Amado, Rees Kassen, Claudia Bank, Alex Wong
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引用次数: 0
摘要
细菌中抗菌素耐药性(AMR)的进化是一个重大的公共卫生问题,为了减少耐药性的传播,通常会采取限制使用抗生素的措施。这些措施的依据是,在没有抗生素的情况下,AMR 变异在生长过程中会产生有害的适应性效应(即成本)。根据这一假设,耐药菌株将在限制期内被不付出代价的易感菌株淘汰。AMR 变异的适应性效应通常是在标准生长环境下生长的实验室参考菌株中进行研究的;然而,遗传和环境背景会影响突变的适应性效应的大小和方向。在本研究中,我们测量了三种变异来源如何影响大肠埃希菌 AMR 突变的适应性效应:抗性突变的类型、宿主的遗传背景和生长环境。我们证明,虽然在无抗生素环境中,AMR 基因突变的代价通常很高,但它们的适存效应差异很大,而且取决于突变、遗传背景和环境之间复杂的相互作用。我们测试了粗糙富士山适应度景观模型在模拟中再现经验数据的能力。我们确定了模型参数,这些参数合理地捕捉到了遗传变异导致的适性效应的变化。然而,在考虑多种生长环境时,该模型无法适应观察到的变化。总之,这项研究揭示了抗性突变的适应性效应因遗传背景和环境条件而产生的巨大差异,这将最终影响它们在自然种群中的持续存在。
Unpredictability of the Fitness Effects of Antimicrobial Resistance Mutations Across Environments in Escherichia coli.
The evolution of antimicrobial resistance (AMR) in bacteria is a major public health concern, and antibiotic restriction is often implemented to reduce the spread of resistance. These measures rely on the existence of deleterious fitness effects (i.e. costs) imposed by AMR mutations during growth in the absence of antibiotics. According to this assumption, resistant strains will be outcompeted by susceptible strains that do not pay the cost during the period of restriction. The fitness effects of AMR mutations are generally studied in laboratory reference strains grown in standard growth environments; however, the genetic and environmental context can influence the magnitude and direction of a mutation's fitness effects. In this study, we measure how three sources of variation impact the fitness effects of Escherichia coli AMR mutations: the type of resistance mutation, the genetic background of the host, and the growth environment. We demonstrate that while AMR mutations are generally costly in antibiotic-free environments, their fitness effects vary widely and depend on complex interactions between the mutation, genetic background, and environment. We test the ability of the Rough Mount Fuji fitness landscape model to reproduce the empirical data in simulation. We identify model parameters that reasonably capture the variation in fitness effects due to genetic variation. However, the model fails to accommodate the observed variation when considering multiple growth environments. Overall, this study reveals a wealth of variation in the fitness effects of resistance mutations owing to genetic background and environmental conditions, which will ultimately impact their persistence in natural populations.
期刊介绍:
Molecular Biology and Evolution
Journal Overview:
Publishes research at the interface of molecular (including genomics) and evolutionary biology
Considers manuscripts containing patterns, processes, and predictions at all levels of organization: population, taxonomic, functional, and phenotypic
Interested in fundamental discoveries, new and improved methods, resources, technologies, and theories advancing evolutionary research
Publishes balanced reviews of recent developments in genome evolution and forward-looking perspectives suggesting future directions in molecular evolution applications.