Antibiotic treatments increasingly fail due to rapid dissemination of drug resistance. Comparative genomics of clinical isolates highlights the role of de novo adaptive mutations and horizontal gene transfer (HGT) in the acquisition of resistance. Yet it cannot fully describe the selective pressures and evolutionary trajectories that yielded today's problematic strains. Experimental evolution offers a compelling addition to such studies because the combination of replicated experiments under tightly controlled conditions with genomics of intermediate time points allows real-time reconstruction of evolutionary trajectories. Recent studies thus established causal links between antibiotic deployment therapies and the course and timing of mutations, the cost of resistance and the likelihood of compensating mutations. They particularly underscored the importance of long-term effects. Similar investigations incorporating horizontal gene transfer (HGT) are wanting, likely because of difficulties associated with its integration into experiments. In this review, we describe current advances in experimental evolution of antibiotic resistance and reflect on ways to incorporate horizontal gene transfer into the approach. We contend it provides a powerful tool for systematic and highly controlled dissection of evolutionary paths to antibiotic resistance that needs to be taken into account for the development of sustainable anti-bacterial treatment strategies.

中文翻译：

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实验进展是剖析抗生素耐药性的有效途径的有效工具。

由于快速传播耐药性，抗生素治疗越来越失败。临床分离株的比较基因组学突显了从头适应性突变和水平基因转移（HGT）在获得抗药性中的作用。然而，它不能完全描述产生当今有问题的应变的选择压力和进化轨迹。实验进化为此类研究提供了令人信服的补充，因为在严格控制的条件下重复实验与中间时间点的基因组学相结合，可以实时重建进化轨迹。因此，最近的研究建立了抗生素部署疗法与突变的过程和时机，耐药性的成本以及补偿突变的可能性之间的因果关系。他们特别强调了长期影响的重要性。希望进行包含水平基因转移（HGT）的类似研究，这可能是由于将其整合到实验中带来的困难。在这篇综述中，我们描述了抗生素抗性实验发展方面的最新进展，并反思了将水平基因转移纳入该方法的方法。我们认为，它为系统性和高度可控地剖析抗生素抗性的进化途径提供了强大的工具，在开发可持续的抗菌治疗策略时需要考虑到这一点。我们描述了抗生素抗性实验发展方面的最新进展，并反思了将水平基因转移纳入该方法的方法。我们认为，它为系统性和高度可控地剖析抗生素抗性的进化途径提供了强大的工具，在开发可持续的抗菌治疗策略时需要考虑到这一点。我们描述了抗生素抗性实验发展方面的最新进展，并反思了将水平基因转移纳入该方法的方法。我们认为，它为系统性和高度可控地剖析抗生素抗性的进化途径提供了强大的工具，在开发可持续的抗菌治疗策略时必须考虑到这一点。