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大肠杆菌对阿莫西林的遗传适应性:dinB和katE的有限作用。

Genetic adaptation to amoxicillin in Escherichia coli: The limited role of dinB and katE.

作者信息

Teichmann Lisa, Wenne Marcus, Luitwieler Sam, Dugar Gaurav, Bengtsson-Palme Johan, Ter Kuile Benno

机构信息

Swammerdam Institute of Life Sciences, Molecular Biology and Microbial Food Safety, University of Amsterdam, Amsterdam, The Netherlands.

Department of Life Sciences, Division of Systems and Synthetic Biology, SciLifeLab, Chalmers University of Technology, Gothenburg, Sweden.

出版信息

PLoS One. 2025 Feb 19;20(2):e0312223. doi: 10.1371/journal.pone.0312223. eCollection 2025.

Abstract

Bacteria can quickly adapt to sub-lethal concentrations of antibiotics. Several stress and DNA repair genes contribute to this adaptation process. However, the pathways leading to adaptation by acquisition of de novo mutations remain poorly understood. This study explored the roles of DNA polymerase IV (dinB) and catalase HP2 (katE) in E. coli's adaptation to amoxicillin. These genes are thought to play essential roles in beta-lactam resistance-dinB in increasing mutation rates and katE in managing oxidative stress. By comparing the adaptation rates, transcriptomic profiles, and genetic changes of wild-type and knockout strains, we aimed to clarify the contributions of these genes to beta-lactam resistance. While all strains exhibited similar adaptation rates and mutations in the frdD gene and ampC operon, several unique mutations were acquired in the ΔkatE and ΔdinB strains. Overall, this study distinguishes the contributions of general stress-related genes on the one hand, and dinB, and katE on the other hand, in development of beta-lactam resistance.

摘要

细菌能够迅速适应亚致死浓度的抗生素。多种应激和DNA修复基因参与了这一适应过程。然而,通过获得从头突变导致适应的途径仍知之甚少。本研究探讨了DNA聚合酶IV(dinB)和过氧化氢酶HP2(katE)在大肠杆菌适应阿莫西林过程中的作用。这些基因被认为在β-内酰胺抗性中发挥重要作用——dinB提高突变率,katE应对氧化应激。通过比较野生型和基因敲除菌株的适应率、转录组图谱和基因变化,我们旨在阐明这些基因对β-内酰胺抗性的贡献。虽然所有菌株在frdD基因和ampC操纵子中表现出相似的适应率和突变,但在ΔkatE和ΔdinB菌株中获得了一些独特的突变。总体而言,本研究区分了一般应激相关基因以及dinB和katE在β-内酰胺抗性形成过程中的贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da7/11838884/f40dd3340032/pone.0312223.g001.jpg

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