title: Comparative genomic analysis of Klebsiella pneumonia (LCT-KP214) and a mutant strain (LCT-KP289) obtained after spaceflight.
abstract: BACKGROUND
  With the development of space science, it is important to analyze the relationship between the space environment and genome variations that might cause phenotypic changes in microbes. Klebsiella pneumoniae is commonly found on the human body and is resistant to multiple drugs. To study space-environment-induced genome variations and drug resistance changes, K. pneumoniae was carried into outer space by the Shenzhou VIII spacecraft.
  
  
  RESULTS
  The K. pneumoniae strain LCT-KP289 was selected after spaceflight based on its phenotypic differences compared to the ground-control strain. Analysis of genomic structural variations revealed one inversion, 25 deletions, fifty-nine insertions, two translocations and six translocations with inversions. In addition, 155 and 400 unique genes were observed in LCT-KP214 and LCT-KP289, respectively, including the gene encoding dihydroxyacetone kinase, which generates the ATP and NADH required for microbial growth. Furthermore, a large number of mutant genes were related to transport and metabolism. Phylogenetic analysis revealed that most genes in these two strains had a dN/dS value greater than 1, indicating that the strain diversity increased after spaceflight. Analysis of drug-resistance phenotypes revealed that the K. pneumoniae strain LCT-KP289 was resistant to sulfamethoxazole, whereas the control strain, LCT-KP214, was not; both strains were resistant to benzylpenicillin, ampicillin, lincomycin, vancomycin, chloramphenicol and streptomycin. The sulfamethoxazole resistance may be associated with sequences in Scaffold7 in LCT-KP289, which were not observed in LCT-K214; this scaffold contained the gene sul1. In the strain LCT-KP289, we also observed a drug-resistance integron containing emrE (confers multidrug resistance) and ant (confers resistance to spectinomycin, streptomycin, tobramycin, kanamycin, sisomicin, dibekacin, and gentamicin). The gene ampC (confers resistance to penicillin, cephalosporin-ii and cephalosporin-i) was present near the integron. In addition, 30 and 26 drug-resistance genes were observed in LCT-KP289 and LCT-KP214, respectively.
  
  
  CONCLUSIONS
  Comparison of a K. pneumoniae strain obtained after spaceflight with the ground-control strain revealed genome variations and phenotypic changes and elucidated the genomic basis of the acquired drug resistance. These data pave the way for future studies on the effects of spaceflight.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Guo
authors.forename: Yinhu
authors.initials: Y
authors.lastname: Li
authors.forename: Longxiang
authors.initials: L
authors.lastname: Su
authors.forename: De
authors.initials: D
authors.lastname: Chang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Yanting
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Fang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Li
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Fang
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Beijing 100853, China. daiwenkui@genomics.cn.
authors.forename: Wenkui
authors.initials: W
authors.lastname: Dai
authors.forename: Changting
authors.initials: C
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D055028:Comparative Genomic Hybridization; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D016680:Genome, Bacterial; D032023:Integrons / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000145:classification / Q000235:genetics*; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013026:Space Flight; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins