Data from: Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across 8 strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across 3 strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds.抗生素耐药性通常通过必需基因保守位点的突变演化形成，可在不同细菌菌株与物种之间引发平行分子演化。然而，此类耐药突变在不同细菌类群中是否会对适合度产生平行影响，目前仍不明确。该问题具有重要研究价值，原因在于耐药突变的适合度效应在病原菌种群的耐药性传播与维持过程中发挥关键作用。 本研究针对该议题展开探究：我们选取了横跨假单胞菌属（Pseudomonas）多样性的8株菌株，测定了其RNA聚合酶β亚基（rpoB）上一系列利福平耐药突变的适合度效应。结果显示，近50%的rpoB突变存在背景依赖性适合度代价，这表明rpoB与基因组其余部分之间的上位相互作用十分普遍。此外，上位效应通常较强，且是决定耐药突变代价的主要遗传因素。 为探究上位效应的功能基础，同时考虑到rpoB在转录过程中发挥核心作用，我们还测定了3株假单胞菌中常见rpoB突变对转录效率的影响。研究发现，不同菌株的转录效率与适合度呈显著相关；而上位效应的产生，是因为单个rpoB突变在不同遗传背景下对转录效率的影响存在差异。