A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress

Osmotic stress is a significant physical challenge for free-living cells. Cells from all three domains of life maintain viability during osmotic stress by tightly regulating the major cellular osmolyte potassium (K(+)) and by import or synthesis of compatible solutes. It has been widely established that in response to high salt stress, many bacteria transiently accumulate high levels of K(+), leading to bacteriostasis, with growth resuming only when compatible solutes accumulate and K(+) levels are restored to biocompatible levels. Using Bacillus subtilis as a model system, we provide evidence that K(+) fluxes perturb Mg(2+) homeostasis: import of K(+) upon osmotic upshift is correlated with Mg(2+) efflux, and Mg(2+) reimport is critical for adaptation. The transient growth inhibition resulting from hyperosmotic stress is coincident with loss of Mg(2+) and a decrease in protein translation. Conversely, the reimport of Mg(2+) is a limiting factor during resumption of growth. Furthermore, we show the essential signaling dinucleotide cyclic di-AMP fluctuates dynamically in coordination with Mg(2+) and K(+) levels, consistent with the proposal that cyclic di-AMP orchestrates the cellular response to osmotic stress.