title: Use of genome sequencing to assess nucleotide structure variation of Staphylococcus aureus strains cultured in spaceflight on Shenzhou-X, under simulated microgravity and on the ground.
abstract: The extreme environment of space could affect microbial behavior and may increase the risk of infectious disease during spaceflight. However, the molecular genetic changes of methicillin-resistant Staphylococcus aureus (MRSA) in response to the spaceflight environment have not been fully clarified. In the present study, we determined the draft genome sequences for an ancestral S. aureus strain (LCT-SAO) isolated from a clinical sample and three derivative strains, LCT-SAS, LCT-SAM and LCT-SAG, cultured in parallel during the spaceflight Shenzhou-X, under simulated microgravity and on the ground, respectively. To evaluate the impact of short-term spaceflight on the MRSA strains, comparative genomic analysis was implemented. Genome-based mapping of toxin genes and antibiotic resistance genes confirmed that these strains have the conventional pathogenicity and resistance to drugs, as none of the strains showed significant changes in these regions after culturing in the three different environments; this result suggests that spaceflight may not change bacterial virulence or drug resistance. Thirty-nine strain-specific sequence variants (SVs) were identified throughout the genomes, and the three derivatives exhibited almost the same mutation rates. Fifty-nine percent of SVs were located in the intergenic regions of the genomes, indicating that S. aureus may have an extremely robust repair mechanism responsible for recognizing and repairing DNA replication mismatches. It is noteworthy that strain LCT-SAS, cultured in space, presented the most unique SVs (n=9) and shared the fewest SVs with LCT-SAM (n=5) and LCT-SAG (n=4). Furthermore, we identified 10 potential deletion regions and 2 potential insertion regions, with LCT-SAS appearing more fragile than other strains by this measure. These results suggest that the environment of space is inherently complicated, with multiple variables, and cannot be simulated in a simple manner. Our results represent the first analysis of nucleotide structure variation of S. aureus strains in a spaceflight environment and also provide a valuable insight for understanding the mutation strategies of MRSA on earth.
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Surveillance and Early-warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing 102206, China; State Key Laboratory for Infectious Disease Prevention and Control, and National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.affiliation: Key Laboratory of Surveillance and Early-warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing 102206, China; State Key Laboratory for Infectious Disease Prevention and Control, and National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Surveillance and Early-warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing 102206, China; State Key Laboratory for Infectious Disease Prevention and Control, and National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
authors.forename: Longxiang
authors.initials: L
authors.lastname: Su
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Surveillance and Early-warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing 102206, China; State Key Laboratory for Infectious Disease Prevention and Control, and National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China. Electronic address: changtingliu301@163.com.
authors.forename: Changting
authors.initials: C
authors.lastname: Liu
mesh_terms: D024881:Drug Resistance, Bacterial / Q000235:genetics; D023061:Gene Order; D005798:Genes, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D054643:INDEL Mutation; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013026:Space Flight; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics; D014893:Weightlessness
chemical_list: D037521:Virulence Factors
keywords: Genome; High-throughput; SNP; Spaceflight; Staphylococcus aureus