Phosphate starvation is accompanied by disturbance of intracellular cysteine homeostasis in Escherichia coli

Metabolic rearrangements that occur during depletion of essential nutrients can lead to accumulation of potentially dangerous metabolites. Here we showed that depletion of phosphate (P_i), accompanied by a sharp inhibition of growth and respiration, caused a transient excess of intracellular cysteine due to a decrease in the rate of protein synthesis. High cysteine level can be dangerous due to its ability to produce ROS and reduce Fe³⁺ to Fenton-reactive Fe²⁺. To prevent these negative effects, excess cysteine was mainly incorporated into glutathione (GSH), the intracellular level of which increased by 3 times, and was also exported to the medium and partially degraded to form H₂S with participation of 3-mercaptopyruvate sulfotransferase (3MST). The addition of P_i to starving cells led to a sharp recovery of respiration and growth, GSH efflux into the medium and K⁺ influx into the cells. A pronounced coupling of P_i, GSH, and K⁺ fluxes was shown upon P_i depletion and addition, which may be necessary to maintain the ionic balance in the cytoplasm. We suggest that processes aimed at restoring cysteine homeostasis may be an integral part of the universal response to stress under different types of stress and for different types of bacteria.