The ability of bacteria to regulate bacteria to regulate ion flux is known to be key for survival. A new study in Cell led by Gürol Süel has shown that regulating magnesium flux also helps protect the ribosomes from antibiotics.
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.
Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival
Dong-yeon D. Lee, Leticia Galera-Laporta, Maja Bialecka-Fornal, Eun Chae Moon, Zhouxin Shen, Steven P. Briggs, Jordi Garcia-Ojalvo & Gürol M. Süel
In Press, Cell: March 7, 2019 DOI:https://doi.org/10.1016/j.cell.2019.01.042