To explore the effects of space on Klebsiella pneumoniae after spaceflights.A strain of Klebsiella pneumoniae was sent to space for 398 hours by ShenZhouⅧ during November 1, 2011, to November 17, 2011.At the same time, a ground simulation with similar temperature conditions during the space flight was performed as a control.After the space mission, the flight and control strains were further analyzed using phenotypic, genomic, transcriptomic and proteomic techniques to explore the divergence of Klebsiella pneumoniae in the space environment.The flight strains LCT-KP289 exhibited a much higher cotrimoxazole resistance level, and changes in metabolism relative to the ground control strain LCT-KP214.After the space flight, 73 SNPs and the copy number variation of the plasmid are identified in the flight stain.Based on the transcriptomic analysis, there are 232 up-regulated genes and 1,879 down-regulated expression genes respectively, which almost belong to metabolism.According to proteomics, there are 57 up-regulated proteins and 125 down-regulated expression proteins.These the differentially expressed proteins were categorized into the following four functions: energy production and conversion, carbohydrate transport and metabolism, translation, ribosomal structure and biogenesis, posttranslational modification, protein turnover, chaperones.From the view of system biology, the ytfG gene is a synonymous mutations, which caused significantly down-regulated expression from both of transciptomic and proteomic levels.In summary, the mutation of ytfG gene may influence the fructose and mannose metabolic process of Klebsiella pneumoniae during space flight, which may beneficial to the field of space microbiology and make potential therapeutic strategies to combat or prevent infection of astronauts.