The antibiotic stress on bacteria leads to initiation of adaptive mechanisms, including exploiting the available opportunity, if any, for cell survival. In order to use the opportunity for survival while under threat, the microbe undergoes various mechanisms which are not completely known e.g. homologous recombination, horizontal gene transfer etc. Our aim is to understand the adaptive mechanism for cell survival during stress, especially antibiotic stress, in E. coli in the presence of opportunity. Understanding this mechanism in bacteria that gained resistance will help in identifying alternative survival pathways. By subjecting a recombination deficient (ΔRecA) strain of bacteria to antibiotic stress, we expected cell death, due to its inability to repair DNA damage (1, 2). Here we show that providing an opportunity in the form of an antibiotic resistance gene with homologous ends aids bacterial survival. There was 3-fold increase in cell envelope thickness along with 2.5-fold increase in phosphatidylethanolamine (PE) content, and enhanced antibiotic resistance to >4000 μg/mL (Kan). We observed genome-wide alteration of methylation pattern that lead to changes in transcriptome, proteome, lipidome, and metabolite level, thus, leading to morphological and physiological changes. We prove that global methylation helps in survival of bacteria under stress that changes essential pathways like energy, cell envelope, lipids, amino acids acid, etc. leading to over production of cell wall components including synthesis of PE. By inhibiting the activity of methyltransferase, it is noticed that there is reduction in PE synthesis in agreement with demethylation. This proves that the phenotypic changes are caused due to the global methylation, and also demonstrates that demethylation could be used as a strategy to prevent antibiotic resistance in microbes.

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通过机会和整体甲基化的细菌表型变化导致抗生素耐药性

细菌对抗生素的压力导致适应机制的启动，包括利用可能的机会存活（如果有的话）。为了利用受到威胁时的生存机会，微生物会经历各种机制，这些机制尚不完全清楚，例如同源重组，水平基因转移等。我们的目的是了解应激（特别是抗生素应激）下细胞存活的适应性机制。大肠杆菌存在的机会。了解获得耐药性的细菌中的这种机制将有助于确定替代的生存途径。通过使重组缺陷（ΔRecA）细菌菌株经受抗生素胁迫，由于其无法修复DNA损伤，我们可以预期细胞死亡（1、2）。在这里，我们显示以具有两端同源性的抗生素抗性基因的形式提供机会有助于细菌存活。细胞膜厚度增加了3倍，磷脂酰乙醇胺（PE）含量增加了2.5倍，对> 4000μg/ mL（Kan）的抗生素耐药性增强。我们观察到甲基化模式的全基因组变化，导致转录组，蛋白质组，脂质组和代谢产物水平发生变化，从而导致形态和生理变化。我们证明，在压力改变能量，细胞包膜，脂质，氨基酸等基本途径的压力下，导致甲基化有助于细菌的存活，从而导致细胞壁成分的过度生产，包括PE的合成。通过抑制甲基转移酶的活性，注意到与去甲基化一致，PE合成减少。这证明了表型的变化是由于总体甲基化引起的，并且还证明了脱甲基可以用作防止微生物对抗生素产生耐药性的策略。