Bacterial populations exhibit heterogeneity in their stress responses. For example, previous studies have shown that a subset of cells can arrest their growth in the presence of antibiotics. Drugs that target active cellular processes, such as ribosome-targeting antibiotics, are less effective in growth-arrested cells, which are thus more likely to survive. In this study, Süel and colleagues investigated whether actively growing cells use specific mechanisms to cope with ribosomal stress induced by antibiotics. In particular, the authors focused on the role of ion flux across the cell membrane in the presence of a ribosome-targeting antibiotic. Bacteria modulate the flux of ions during stress, which leads to changes in the cellular membrane potential, but whether bacteria modify ion flux in the presence of antibiotics, whether the modulation of ion flux under stress conditions differs between individual cells and how this response relates to survival were not well understood.
Next, the authors analysed protein levels and found that in the L22* strain, ion transporters were upregulated, in particular magnesium transporters. In addition, the L22* strain had higher intracellular magnesium concentrations compared with the wild-type strain. As magnesium ions stabilize the structure of the ribosome, the authors suggested that increased expression of magnesium transporters leads to increased intracellular magnesium levels, which decreases hyperpolarization and increases cell growth and survival possibly owing to increased stability of the ribosome complex. In agreement with this hypothesis, the addition of excess magnesium ions to the growth medium reduced hyperpolarization in wild-type cells in the presence of the antibiotic. By contrast, other cations, such as potassium, sodium or calcium, were less effective at reducing hyperpolarization, which is in agreement with the finding that mainly magnesium transporters were upregulated under ribosomal stress conditions. Moreover, increasing the concentration of magnesium in the growth medium reduced hyperpolarization of the L34-deletion strain and rescued the growth defect.
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