背景：
细菌获得抗生素抗性的能力在很大程度上依赖于它们的基因组修饰能力。原核基因组具有高度可塑性，可利用水平基因转移，点突变和基因缺失或扩增来实现基因组扩增和重排。点突变对从头获得抗生素抗性的贡献是公认的。在这项研究中，使用全基因组测序研究了在从头获得抗生素抗性期间大肠杆菌的内部基因组重排。

结果：
使细胞对四种抗生素中的一种产生抗性，然后对剩余的三种抗生素中的一种产生抗性。这样，最初的遗传重排可以与遗传背景改变对抗药性后续发展的影响一起记录。由于暴露于阿莫西林，包括ampC的DNA片段被有时超过100的因子扩增。在具有双重暴露史的许多样品中观察到原噬菌体e14的切除，但是在暴露于单一抗生素的细胞中没有观察到，表明单独的SOS应激反应的激活（通常是切除的触发因素）不足以引起原噬菌体的切除。 E14。在暴露于恩诺沙星和四环素的菌株中发生clpS和clpA的部分缺失。在一些菌株中观察到其他缺失，但在具有完全相同的暴露历史的重复中没有观察到。各种插入序列转座与暴露于特定抗生素相关。

结论：
许多基因组重排之前尚未报道在抗性发展期间发生。观察到的基因组重排与特定抗生素压力之间的相关性以及它们在独立重复中的存在表明这些事件不是随机发生的。总之，观察到的基因组重排说明了当暴露于抗生素胁迫时大肠杆菌基因组的可塑性。

BACKGROUND:
The ability of bacteria to acquire resistance to antibiotics relies to a large extent on their capacity for genome modification. Prokaryotic genomes are highly plastic and can utilize horizontal gene transfer, point mutations, and gene deletions or amplifications to realize genome expansion and rearrangements. The contribution of point mutations to de novo acquisition of antibiotic resistance is well-established. In this study, the internal genome rearrangement of Escherichia coli during to de novo acquisition of antibiotic resistance was investigated using whole-genome sequencing.

RESULTS:
Cells were made resistant to one of the four antibiotics and subsequently to one of the three remaining. This way the initial genetic rearrangements could be documented together with the effects of an altered genetic background on subsequent development of resistance. A DNA fragment including ampC was amplified by a factor sometimes exceeding 100 as a result of exposure to amoxicillin. Excision of prophage e14 was observed in many samples with a double exposure history, but not in cells exposed to a single antibiotic, indicating that the activation of the SOS stress response alone, normally the trigger for excision, was not sufficient to cause excision of prophage e14. Partial deletion of clpS and clpA occurred in strains exposed to enrofloxacin and tetracycline. Other deletions were observed in some strains, but not in replicates with the exact same exposure history. Various insertion sequence transpositions correlated with exposure to specific antibiotics.

CONCLUSIONS:
Many of the genome rearrangements have not been reported before to occur during resistance development. The observed correlation between genome rearrangements and specific antibiotic pressure, as well as their presence in independent replicates indicates that these events do not occur randomly. Taken together, the observed genome rearrangements illustrate the plasticity of the E. coli genome when exposed to antibiotic stress.

https://www.ncbi.nlm.nih.gov/pubmed/30591014