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探讨复苏应激反应、突变和恢复期间耐药性之间的联系。

Exploring the links between SOS response, mutagenesis, and resistance during the recovery period.

机构信息

Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA.

出版信息

Antimicrob Agents Chemother. 2024 May 2;68(5):e0146223. doi: 10.1128/aac.01462-23. Epub 2024 Mar 27.

Abstract

Although the mechanistic connections between SOS-induced mutagenesis and antibiotic resistance are well established, our current understanding of the impact of SOS response levels, recovery durations, and transcription/translation activities on mutagenesis remains relatively limited. In this study, when bacterial cells were exposed to mutagens like ultraviolet light for defined time intervals, a compelling connection between the rate of mutagenesis and the RecA-mediated SOS response levels became evident. Our observations also indicate that mutagenesis primarily occurs during the subsequent recovery phase following the removal of the mutagenic agent. When transcription/translation was inhibited or energy molecules were depleted at the onset of treatment or during the early recovery phase, there was a noticeable decrease in SOS response activation and mutagenesis. However, targeting these processes later in the recovery phase does not have the same effect in reducing mutagenesis, suggesting that the timing of inhibiting transcription/translation or depleting energy molecules is crucial for their efficacy in reducing mutagenesis. Active transcription, translation, and energy availability within the framework of SOS response and DNA repair mechanisms appear to be conserved attributes, supported by their consistent manifestation across diverse conditions, including the use of distinct mutagens such as fluoroquinolones and various bacterial strains.

摘要

虽然 SOS 诱导的突变和抗生素耐药性之间的机制联系已经得到很好的确立,但我们对 SOS 反应水平、恢复持续时间和转录/翻译活性对突变的影响的理解仍然相对有限。在这项研究中,当细菌细胞暴露于紫外线等诱变剂时,在定义的时间间隔内,突变率和 RecA 介导的 SOS 反应水平之间存在着强烈的联系。我们的观察还表明,突变主要发生在去除诱变剂后的后续恢复阶段。当在处理开始时或早期恢复阶段抑制转录/翻译或耗尽能量分子时,SOS 反应的激活和突变明显减少。然而,在恢复阶段后期靶向这些过程并不能同样有效地减少突变,这表明抑制转录/翻译或耗尽能量分子的时机对于降低突变的效果至关重要。在 SOS 反应和 DNA 修复机制的框架内,活跃的转录、翻译和能量供应似乎是保守的特征,这一特征在不同的条件下都得到了一致的表现,包括使用不同的诱变剂,如氟喹诺酮类药物和各种细菌菌株。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02a7/11064565/6dbe93d77a70/aac.01462-23.f001.jpg

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