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Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival
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Bacteria exhibit cell-to-cell variability in their resilience to stress, for example, following antibiotic exposure. Higher resilience is typically ascribed to "dormant" non-growing cellular states. Here, by measuring membrane potential dynamics of Bacillus subtilis cells, we show that actively growing bacteria can cope with ribosome-targeting antibiotics through an alternative mechanism based on ion flux modulation. Specifically, we observed two types of cellular behavior: growth-defective cells exhibited a mathematically predicted transient increase in membrane potential (hyperpolarization), followed by cell death, whereas growing cells lacked hyperpolarization events and showed elevated survival. Using structural perturbations of the ribosome and proteomic analysis, we uncovered that stress resilience arises from magnesium influx, which prevents hyperpolarization. Thus, ion flux modulation provides a distinct mechanism to cope with ribosomal stress. These results suggest new approaches to increase the effectiveness of ribosome-targeting antibiotics and reveal an intriguing connection between ribosomes and the membrane potential, two fundamental properties of cells.
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“These data, together with recent publications highlighting the connection between Mg2+ homeostasis and translation (29, 33, 34), support the idea that a decrease in Mg2+ during osmoadaptation could impair translation and thereby delay the resumption of growth.”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [34]
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Metadata
- Authors
- Lee, D.-Y. D., Galera-Laporta, L., Bialecka-Fornal, M., Moon, E. C., Shen, Z., Briggs, S. P., Garcia-Ojalvo, J., & Süel, G. M.
- Affiliations
- University of California San Diego (US)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Süel, Gürol M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 177
- Issue
- 2
- Pages
- 352-360.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6814349
- OpenAlex
- W2922356758
- Cited by
- 147
- References
- 46
- Citations by year
- 2026: 27 · 2025: 24 · 2024: 20 · 2023: 15 · 2022: 24 · 2021: 23 · 2020: 7 · 2019: 7
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (acceptedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion)
- Funders
- Spanish Ministry of Economy and Competitiveness
- FEDER (FIS2015-66503-C3-1-P)
- ICREA
- Maria de Maeztu Program for Units of Excellence in Research and Development (MDM-2014-0370)
- San Diego Center for Systems Biology
- NIH (P50 GM085764)
- National Institute of General Medical Sciences (R01 GM121888)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- magnesium influx, ribosome-targeting antibiotics, membrane hyperpolarization, Bacillus subtilis, cell-to-cell variability, antibiotic tolerance
- MeSH terms
- Bacterial Outer Membrane, Bacillus subtilis, Bacterial Proteins, Magnesium, Ribosomal Proteins, Ribosomes, Proteomics
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