| Infections caused by various kinds of pathogenic microorganisms are the most common and multiple human diseases. With the extensive use of broad-spectrum antibiotics, drug-resistance of bacteria and secondary infections due to the drug-resistance have made clinical treatment extremely difficult, and also caused huge pressure and burden to society and family economy. Currently, multidrug-resistant bacteria (such as Escherichia coli, E. coli) are spreading worldwide, which has posed a great threat to public health. The consequence can be even worse than ever expected. Although the studies of bacterial resistance are relatively in-depth and wide-ranging, the results still remain precarious. New research methods are urgently needed. As the flourish of China’s aerospace industry, the development created new opportunities to space-biomedical research. Microgravity, extreme temperature difference, particle radiation and other factors in the radiation environment of space can induce phenotype changes of pathogen biological character, like virulence and drug resistance. It provides a brand new platform for the study of pathogenic microorganisms. In this study, we isolated an E. coli strain from the sputum of an elderly patient with pulmonary infection. This strain was found to be resistant to 15 out of 17 commonly used clinical antibiotics including fourth-generation cephalosporins, fluoroquinolones and carbapenems. Through analysis of whole-genome sequencing, it was found that 51 genes (including 21 types of drug efflux pumps) associated with resistance to commonly used antibiotics, like aminoglycosides, beta-lactams, fluoroquinolones, tetracyclines, sulphonamides, and so on. Practically, these genes cover all possibilities of known drug-resistance mechanisms in E.coli. Insertion sequence (IS) analysis revealed that 47 resistant genes were flanked by insertion sequence, suggestive of feasible gene exchange among bacteria, which can exacerbate drug resistance of many pathogens clinically. Then we sent this E. coli to outer space by China’s Shenzhou X spacecraft. After 15 days’ travelling in the space, it was found that the total cell number was only 27.7% of that in the same strain cultivated on the earth. Metabolic experiment data revealed its defect in carbon source utilization. These results manifested that short-term spaceflight went against to the E. coli growth and propagation. Drug susceptibility experiment revealed that it got sensitive to tobramycin from resistance to it after spaceflight. Then through high-throughput sequencing analysis on genome, transcriptome, and proteome, we found that 38 single nucleotide polymorphism (SNP) appeared in the E.coli genome after space flight. They are located in 9 intergenic regions and on 20 genes. These genes are related to drug-resistance, environmental response, metabolism, deoxyribonucleic acid (DNA) replication and repair, and etc. Some genes related to energy metabolism, and ATP-binding cassette transporter (ABC) were significantly reduced in transcription and protein level. These changes tend to be identical with phenotypic changes results. By experiment and research, it is pointed out that,1. Drug-resistance of E. coli is a crucial and probably more aggravating problem waiting us to resolve.2. Spaceflight poses great effects on phenotypes of E. coli, like drug-resistance. The research on microbial phenotype and molecular mechanism in the use of spaceflight will provide new guidance on how to control refractory infection on the earth.3. Spaceflight is adverse to the growth of E. coli, which is a part of the human intestinal flora. To further study its phenomena and potential mechanisms can provide guidance on astronauts’health protection in orbit. |
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