Multiple antibiotic resistances are a major global health threat. The predominant tool for adaptation in Gram-negative bacteria is the integron. Under stress, it rearranges gene cassettes to offer an escape using the tyrosine recombinase IntI, recognizing folded DNA hairpins, the attC sites. Four recombinases and two attC sites form the synaptic complex. Yet, for unclear reasons, the recombination efficiency varies greatly. Here, we established an optical tweezers force spectroscopy assay to probe the synaptic complex stability and revealed, for seven combinations of attC sites, significant variability in the mechanical stability. We found a strong correlation between mechanical stability and recombination efficiency of attC sites in vivo, indicating a regulatory mechanism from the DNA structure to the macromolecular complex stability. Taking into account known forces during DNA metabolism, we propose that the variation of the integron in vivo recombination efficiency is mediated by the synaptic complex stability. We anticipate that further recombination processes are also affected by their corresponding mechanical stability.

中文翻译：

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细菌整合子的重组效率取决于突触复合物的机械稳定性


多种抗生素耐药性是一个主要的全球健康威胁。革兰氏阴性细菌适应的主要工具是整合子。在压力下，它重新排列基因盒以使用酪氨酸重组酶 IntI 提供逃逸，识别折叠的 DNA 发夹，即 attC 位点。四个重组酶和两个 attC 位点形成突触复合物。然而，由于不清楚的原因，复合效率差异很大。在这里，我们建立了一种光镊力光谱测定法来探测突触复合物的稳定性，并揭示了 attC 位点的七种组合，机械稳定性的显着可变性。我们发现体内 attC 位点的机械稳定性和重组效率之间存在很强的相关性，表明从 DNA 结构到大分子复合物稳定性的调节机制。考虑到 DNA 代谢过程中的已知力，我们提出整合子体内重组效率的变化是由突触复合物稳定性介导的。我们预计进一步的复合过程也会受到其相应机械稳定性的影响。