Bacterial antibiotic resistance sets a great challenge to human health. It seems that the bacteria can spontaneously evolve resistance against any antibiotic within short time without the horizontal transfer of heterologous genes and before accumulating drug-resistant mutations. We have shown that the tRNA-mediated translational regulation counteracts the reactive oxygen species in bacteria. In this study, we demonstrated that isolated and subcultured Escherichia coli elevated its tRNAs under antibiotic stress to rapidly provide antibiotic resistance, especially at the early stage, before upregulating the efflux pump and evolving resistance mutations. The DNA recombination system repaired the antibiotic-induced DNA breakage in the genome, causing numerous structural variations. These structural variations are overrepresented near the tRNA genes, which indicated the cause of tRNA up-regulation. The strains knocking out the recombination system could not up-regulate tRNAs, and coincidently, they could hardly evolve antibiotic resistance in multiple antibiotics, respectively. With these results, we proposed a multi-stage model of bacterial antibiotic resistance in an isolated scenario: the early stage (recombination – tRNA up-regulation – translational regulation); the medium stage (up-regulation of efflux pump); the late stage (resistance mutations). These results also indicated that the bacterial DNA recombination system and tRNA could be targeted to retard the bacterial spontaneous drug resistance.

中文翻译：

---

基因组重组介导的tRNA上调可在早期对细菌产生一般的抗生素抗性

细菌抗药性对人类健康提出了巨大挑战。似乎细菌可以在短时间内自发地产生对任何抗生素的抗性，而无需异源基因的水平转移，并且可以在积累耐药性突变之前。我们已经表明，tRNA介导的翻译调节抵消细菌中的活性氧。在这项研究中，我们证明了分离和继代培养的大肠杆菌在抗生素胁迫下提高了其tRNA，以快速提供抗生素耐药性，尤其是在早期，在上调外排泵和进化耐药突变之前。DNA重组系统修复了抗生素诱导的基因组DNA断裂，从而导致许多结构变异。这些结构变异在tRNA基因附近过分表达，这表明了tRNA上调的原因。敲除重组系统的菌株不能上调tRNA，巧合的是，它们几乎不能分别对多种抗生素产生耐药性。有了这些结果，我们提出了一个孤立场景中细菌抗生素耐药性的多阶段模型：早期阶段（重组– tRNA上调–翻译调控）；中间阶段（外排泵的上调）；晚期（电阻突变）。这些结果还表明，细菌DNA重组系统和tRNA可以靶向延缓细菌自发耐药性。它们几乎很难分别对多种抗生素产生抗药性。有了这些结果，我们提出了一个孤立场景中细菌抗生素耐药性的多阶段模型：早期阶段（重组– tRNA上调–翻译调控）；中间阶段（外排泵的上调）；晚期（电阻突变）。这些结果还表明，细菌DNA重组系统和tRNA可以靶向延缓细菌自发耐药性。它们几乎很难分别对多种抗生素产生抗药性。有了这些结果，我们提出了一个孤立场景中细菌抗生素耐药性的多阶段模型：早期阶段（重组– tRNA上调–翻译调控）；中间阶段（外排泵的上调）；晚期（电阻突变）。这些结果还表明，细菌DNA重组系统和tRNA可以靶向延缓细菌自发耐药性。