Role of RelA-synthesized (p)ppGpp and ROS-induced mutagenesis in de novo acquisition of antibiotic resistance in E. coli .
| Autor: | Qi W; Laboratory for Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands., Jonker MJ; RNA Biology & Applied Bioinformatics, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands., de Leeuw W; RNA Biology & Applied Bioinformatics, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands., Brul S; Laboratory for Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands., Ter Kuile BH; Laboratory for Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | IScience [iScience] 2024 Mar 26; Vol. 27 (4), pp. 109579. Date of Electronic Publication: 2024 Mar 26 (Print Publication: 2024). |
| DOI: | 10.1016/j.isci.2024.109579 |
| Abstrakt: | The stringent response of bacteria to starvation and stress also fulfills a role in addressing the threat of antibiotics. Within this stringent response, (p)ppGpp, synthesized by RelA or SpoT, functions as a global alarmone. However, the effect of this (p)ppGpp on resistance development is poorly understood. Here, we show that knockout of relA or rpoS curtails resistance development against bactericidal antibiotics. The emergence of mutated genes associated with starvation and (p)ppGpp, among others, indicates the activation of stringent responses. The growth rate is decreased in Δ relA -resistant strains due to the reduced ability to synthesize (p)ppGpp and the persistence of deacylated tRNA impeding protein synthesis. Sluggish cellular activity causes decreased production of reactive oxygen species (ROS), thereby reducing oxidative damage, leading to weakened DNA mismatch repair, potentially reducing the generation of mutations. These findings offer new targets for mitigating antibiotic resistance development, potentially achieved through inhibiting (p)ppGpp or ROS synthesis. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).) |
| Databáze: | MEDLINE |
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