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Hyper-osmotic stress is one of the key factors that decrease the efficiency of biological succinic acid production. To increase the osmotic stress tolerance of succinate-producing Escherichia coli, we studied the influence of IrrE, an exogenous global regulator, on cell osmotic stress resistance. Fermentation results showed that cell growth and succinic acid production by the recombinant increased under different Na+ concentrations. Meanwhile, the maximum dry cell mass, glucose consumption and succinic acid concentration increased 15.6%, 22% and 23%, respectively, when fermented in a 5-L bioreactor. Expressing IrrE improved cell resistance to hyper-osmotic stress. Further comparison of intracellular osmoprotectants (trehalose and glycerol) concentrations showed that trehalose and glycerol concentrations in the recombinant increased. This suggested that introduction of IrrE could enhance intracellular osmoprotectants accumulation which conferred cell with improved resistance to osmotic stress.