Academic Journal
Mutations in respiratory complex I promote antibiotic persistence through alterations in intracellular acidity and protein synthesis.
| العنوان: | Mutations in respiratory complex I promote antibiotic persistence through alterations in intracellular acidity and protein synthesis. |
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| المؤلفون: | Van den Bergh, B, Schramke, H, Michiels, JE, Kimkes, TEP, Radzikowski, JL, Schimpf, J, Vedelaar, SR, Burschel, S, Dewachter, L, Lončar, N, Schmidt, A, Meijer, T, Fauvart, M, Friedrich, T, Michiels, J, Heinemann, M |
| المصدر: | 17 ; 1 |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2022 |
| المجموعة: | Imperial College London: Spiral |
| جغرافية الموضوع: | England |
| الوصف: | Antibiotic persistence describes the presence of phenotypic variants within an isogenic bacterial population that are transiently tolerant to antibiotic treatment. Perturbations of metabolic homeostasis can promote antibiotic persistence, but the precise mechanisms are not well understood. Here, we use laboratory evolution, population-wide sequencing and biochemical characterizations to identify mutations in respiratory complex I and discover how they promote persistence in Escherichia coli. We show that persistence-inducing perturbations of metabolic homeostasis are associated with cytoplasmic acidification. Such cytoplasmic acidification is further strengthened by compromised proton pumping in the complex I mutants. While RpoS regulon activation induces persistence in the wild type, the aggravated cytoplasmic acidification in the complex I mutants leads to increased persistence via global shutdown of protein synthesis. Thus, we propose that cytoplasmic acidification, amplified by a compromised complex I, can act as a signaling hub for perturbed metabolic homeostasis in antibiotic persisters. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| Relation: | Nature Communications; http://hdl.handle.net/10044/1/94575 |
| DOI: | 10.1038/s41467-022-28141-x |
| الاتاحة: | http://hdl.handle.net/10044/1/94575 https://doi.org/10.1038/s41467-022-28141-x |
| Rights: | © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.A20213F3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-022-28141-x |