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利用基因组测序评估神舟十号太空飞行、模拟微重力及地面条件下培养的金黄色葡萄球菌菌株的核苷酸结构变异。

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.

作者信息

Guo Jun, Han Na, Zhang Yuanyuan, Wang Haiyin, Zhang Xuelin, Su Longxiang, Liu Chao, Li Jia, Chen Chen, Liu Changting

机构信息

Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, China.

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.

出版信息

Microbiol Res. 2015 Jan;170:61-8. doi: 10.1016/j.micres.2014.09.001. Epub 2014 Sep 16.

DOI:10.1016/j.micres.2014.09.001
PMID:25304992
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.

摘要

太空的极端环境可能会影响微生物行为,并可能增加太空飞行期间传染病的风险。然而,耐甲氧西林金黄色葡萄球菌(MRSA)在太空飞行环境中的分子遗传变化尚未完全阐明。在本研究中,我们确定了从临床样本中分离出的一株祖先金黄色葡萄球菌菌株(LCT-SAO)以及三个衍生菌株LCT-SAS、LCT-SAM和LCT-SAG的基因组草图序列,这三个衍生菌株分别是在神舟十号太空飞行期间、模拟微重力条件下以及地面上平行培养得到的。为了评估短期太空飞行对MRSA菌株的影响,我们进行了比较基因组分析。基于基因组的毒素基因和抗生素抗性基因图谱证实,这些菌株具有常规的致病性和耐药性,因为在三种不同环境中培养后,这些区域的菌株均未显示出显著变化;这一结果表明太空飞行可能不会改变细菌的毒力或耐药性。在整个基因组中鉴定出了39个菌株特异性序列变异(SVs),三个衍生物表现出几乎相同的突变率。59%的SVs位于基因组的基因间区域,这表明金黄色葡萄球菌可能具有极其强大的修复机制,负责识别和修复DNA复制错配。值得注意的是,在太空中培养的菌株LCT-SAS呈现出最独特的SVs(n = 9),与LCT-SAM(n = 5)和LCT-SAG(n = 4)共享的SVs最少。此外,我们鉴定出10个潜在的缺失区域和2个潜在的插入区域,通过这一指标衡量,LCT-SAS比其他菌株显得更脆弱。这些结果表明,太空环境本质上是复杂的,存在多个变量,无法以简单的方式进行模拟。我们的结果代表了对太空飞行环境中金黄色葡萄球菌菌株核苷酸结构变异的首次分析,也为理解地球上MRSA的突变策略提供了有价值的见解。

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