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Cell. 2019 Apr 4;177(2):352-360.e13. doi: 10.1016/j.cell.2019.01.042. Epub 2019 Mar 7.

Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival.

Author information

1
Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
2
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
3
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093-0380, USA.
4
Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA; San Diego Center for Systems Biology, University of California, San Diego, La Jolla, CA 92093-0380, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093-0380, USA. Electronic address: gsuel@ucsd.edu.

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.

KEYWORDS:

antibiotics; bacterial survival; cations; ion flux; ion transporters; magnesium; membrane potential; ribosomes; single-cell dynamics

PMID:
30853217
DOI:
10.1016/j.cell.2019.01.042

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