Magnesium flux modulates ribosomes to increase bacterial survival

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• dc.contributor.author Lee, Dong-yeon D.
• dc.contributor.author Galera Laporta, Letícia, 1985-
• dc.contributor.author Bialecka-Fornal, Maja
• dc.contributor.author Moon, Eun Chae
• dc.contributor.author Shen, Zhouxin
• dc.contributor.author Briggs, Steven P.
• dc.contributor.author García Ojalvo, Jordi
• dc.contributor.author Süel, Gürol M.
• dc.date.accessioned 2019-07-10T07:24:42Z
• dc.date.issued 2019
• dc.description.abstract 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.
• dc.description.sponsorship This work was supported by funding from The Spanish Ministry of Economy and Competitiveness and FEDER (project FIS2015-66503-C3-1-P) (to J.G.-O.), the ICREA Academia program (to J.G.-O.), and the Maria de Maeztu Program for Units of Excellence in Research and Development (Spanish Ministry of Economy and Competitiveness, MDM-2014-0370) (to J.G.-O.), the San Diego Center for Systems Biology (NIH P50 GM085764) (to G.M.S), National Institute of General Medical Sciences (R01 GM121888) (to G.M.S), and the Howard Hughes Medical Institute-Simons Foundation Faculty Scholars program (to G.M.S.).
• dc.format.mimetype application/pdf
• dc.identifier.citation Lee DD, Galera-Laporta L, Bialecka-Fornal M, Moon EC, Shen Z, Briggs SP, Garcia-Ojalvo J, Süel GM. Magnesium flux modulates ribosomes to increase bacterial survival. Cell. 2019; 177(2):352-60. DOI: 10.1016/j.cell.2019.01.042
• dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2019.01.042
• dc.identifier.issn 0092-8674
• dc.identifier.uri http://hdl.handle.net/10230/41975
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell. 2019; 177(2):352-60
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/FIS2015-66503-C3-1-P
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.cell.2019.01.042
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Antibiotics
• dc.subject.keyword Bacterial survival
• dc.subject.keyword Cations
• dc.subject.keyword Ion flux
• dc.subject.keyword Ion transporters
• dc.subject.keyword Magnesium
• dc.subject.keyword Membrane potential
• dc.subject.keyword Ribosomes
• dc.subject.keyword Single-cell dynamics
• dc.title Magnesium flux modulates ribosomes to increase bacterial survival
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion