Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains
Year: 2018
Type: article
Abstract: BACKGROUND: The antimicrobial resistance (AMR) phenotypic properties, multiple drug resistance (MDR) gene profiles, and genes related to potential virulence and pathogenic properties of five Enterobacter bugandensis strains isolated from the International Space Station (ISS) were carried out and compared with genomes of three clinical strains. Whole genome sequences of ISS strains were characterized using the hybrid de novo assembly of Nanopore and Illumina reads. In addition to traditional microbial taxonomic approaches, multilocus sequence typing (MLST) analysis was performed to classify the phylogenetic lineage. Agar diffusion discs assay was performed to test antibiotics susceptibility. The draft genomes after assembly and scaffolding were annotated with the Rapid Annotations using Subsystems Technology and RNAmmer servers for downstream analysis. RESULTS: and two clinical isolates (153_ECLO and MBRL 1077). Comparative genomic analyses of all eight E. bungandensis strains showed, a total of 4733 genes were associated with carbohydrate metabolism (635 genes), amino acid and derivatives (496 genes), protein metabolism (291 genes), cofactors, vitamins, prosthetic groups, pigments (275 genes), membrane transport (247 genes), and RNA metabolism (239 genes). In addition, 112 genes identified in the ISS strains were involved in virulence, disease, and defense. Genes associated with resistance to antibiotics and toxic compounds, including the MDR tripartite system were also identified in the ISS strains. A multiple antibiotic resistance (MAR) locus or MAR operon encoding MarA, MarB, MarC, and MarR, which regulate more than 60 genes, including upregulation of drug efflux systems that have been reported in Escherichia coli K12, was also observed in the ISS strains. CONCLUSION: Given the MDR results for these ISS Enterobacter genomes and increased chance of pathogenicity (PathogenFinder algorithm with > 79% probability), these species pose important health considerations for future missions. Thorough genomic characterization of the strains isolated from ISS can help to understand the pathogenic potential, and inform future missions, but analyzing them in in-vivo systems is required to discern the influence of microgravity on their pathogenicity.
Source: BMC Microbiology
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funders: National Aeronautics and Space Administration, Bill and Melinda Gates Foundation, Alfred P. Sloan Foundation, California Institute of Technology, Vallee Foundation, WorldQuant Foundation, National Institutes of Health, Ames Research Center, Jet Propulsion Laboratory, Weill Cornell Medical College, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences
Awards: G110959122, G1284901464, G1575842294, (1) SUMMARYMASSIVELY PARALLEL DNA SEQUENCING CONTINUES TO PROVIDE ASTONISHING INSIGHTS INTO THE REGULATORY COMPLEXITY OF THE MAMMALIAN GENOME REVEALING HERITABLE AND DE NOVO OCCURRING RISK FACTORS PREDISPOSING HUMANS TO A WIDE VARIETY OF DISEASES AND DISORDERS. NOTABLY MEMBERS OF THE ENCYCLOPEDIA OF DNA ELEMENTS (ENCODE) CONSORTIUM INCLUDING CO-INVESTIGATORS DRS. MASON AND SNYDER HAVE RECENTLY MAPPED THOUSANDS OF NON-CODING REGULATORY ELEMENTS IN THE HUMAN GENOME THAT SPECIFY RISK AND PROTECTIVE SITES FOR MANY DISEASE. THESE NONCODING GENETIC VARIATIONS ALSO SHOW DIFFERENTIAL IMPACT DEPENDING ON THE EPIGENETIC CHANGES OF THE GENOME INCLUDING METHYLATION OF DNA AND CHROMATIN STATES INSIDE CELLS. YET THESE QUESTIONS HAVE NOT BEEN COMPREHENSIVELY EXAMINED IN HUMAN ASTRONAUTS DUE TO THE FACT THAT THE VERY FIRST DATA SETS THAT CAN DELINEATE THE PUTATIVE IMPACT OF GENOME-WIDE NONCODING VARIATION AND EPIGENETIC CHANGES FROM SPACE TRAVEL ARE ONLY NOW BEING GENERATED IN THE NASA TWINS STUDY.HOWEVER WITH THIS DATA FROM NASA TWINS STUDY THERE IS A UNIQUE OPPORTUNITY TO BOTH GENERATE NEW COMPUTATIONAL TOOLS FOR THE INTEGRATION OF THE DATA FROM THESE SAMPLES AND ALSO TO UTILIZE NOVEL SINGLE-CELL APPROACHES FOR EPIGENETIC STATES IN THE HUMAN CELLS TAKEN FROM SPACE. WE PROPOSE TO EXPAND AND FURTHER INTEGRATE OUR TOOLS FOR EXAMINING THE REGULATORY CHANGES TO DNA AND RNA TOGETHER CALLED "EPISUITE " WHICH WILL PROVIDE LONG-SOUGHT SOLUTIONS TO PROBLEMS IN INTEGRATIVE GENOMICS AND ESTABLISH A MORE SYSTEMS-LEVEL VIEW OF HUMAN PHYSIOLOGY DURING SPACE TRAVEL. SPECIFICALLY WE WILL OPTIMIZE AND INTEGRATE OPEN-SOURCE AND PUBLISHED BIOINFORMATICS TOOLS BETWEEN BOTH LABORATORIES (HUGE-SEQ METHYLKIT EDMR R-MAKE) EXPAND OUR CODE BASE WITH TWO NEW TOOLS (METHCLONE AND CEMBASE) AND THEN CREATE A WEB-INTERFACE FOR USERS TO UPLOAD ORGANIZE AND ANALYZE THESE DATA RELATIVE TO ENCODE PUBLIC DATA. THEN WE WILL USE NOVEL SINGLE-CELL EXPERIMENTAL METHODS (SCATAC-SEQ) TO CONFIRM AND CHARACTERIZE THE IMPACT AND SCOPE OF SUCH NONCODING AND EPIGENETIC CHANGES. TOGETHER THE DATA AND TOOLS IN EPISUITE CONCOMITANT WITH THE NEW SINGLE-CELL CHROMATIN DATA WILL ENABLE DISCOVERY AND VALIDATION OF SPECIFIC LOCI THAT REPRESENT THE GENETIC AND EPIGENETIC RISKS FACED BY ASTRONAUTS AND ALSO AN IMPROVED UNDERSTANDING OF THE REGULATORY AND GENETIC IMPACT (BMED5) OF THESE MOLECULAR CHANGES.(2) HYPOTHESISWE HYPOTHESIZE THAT SPECIFIC AREAS OF THE GENOME ARE EPIGENETICALLY DYSREGULATED AS A RESULT OF SPACE TRAVEL AND THAT SOME OF THESE AREAS DIFFER BETWEEN ASTRONAUTS. MOREOVER WE HYPOTHESIZE THAT THE ENRICHMENT OF NON-CODING VARIANTS IN DISTINCT BIOLOGICAL PATHWAYS WILL ALSO DIFFER BETWEEN ASTRONAUTS AND ANALYSIS AND INTEGRATION OF THESE DATA WILL REVEAL THE FIRST REGIONS OF "EPIGENETIC SPACE RISK" FOR THE ASTRONAUTS DELINEATED IN BMED5. TO VALIDATE THESE PREDICTIONS WE WILL PERFORM SINGLE-CELL ATAC-SEQ (ASSAY FOR TRANSPOSASE ACCESSIBLE CHROMATIN) ON CELL FRACTIONS FROM EARTH-BASED CONTROL SAMPLES AND THOSE TAKEN FROM SPACE.(3) SPECIFIC AIMSAIM 1. CREATE A WEB-BASED FRAMEWORK FOR INTEGRATING NON-CODING GENOMIC VARIATION AND DIFFERENTIAL EPIGENETIC STATES. THIS EPISUITE INTERFACE AND SET OF MACHINE-LEARNING ALGORITHMS WILL HELP ONGOING WORK WITH THE NASA TWINS STUDY AND AID FUTURE INVESTIGATIONS THAT LEVERAGE MULTI-OMICS DATA SETS FROM ASTRONAUTS. THESE DATA WILL ALSO BE LINKED TO GENE EXPRESSION DATA TO GAUGE THE IMPACT OF GENETIC AND EPIGENETIC CHANGES ON SPECIFIC BIOLOGICAL NETWORKS.AIM 2. VALIDATE THE ALTERED CHROMATIN STATES IN CELLS FROM SPACE TRAVEL AND MEASURE THE PROPORTION OF CELLS CHANGED WITH SINGLE-CELL ATAC-SEQ. WE WILL USE AN ASSAY CALLED SINGLE CELL (SCATAC-SEQ) WHICH CAN MEASURE THE SITES OF OPEN AND CLOSED CHROMATIN ON A CELL-BY-CELL BASIS. THIS WILL VALIDATE THE SITES WHERE WE OBSERVE EPIGENETIC CHANGES AND ALSO PROVIDE THE FIRST ESTIMATE OF THE PROPORTION OF CELLS EPIGENETICALLY IMPACTED BY SPACE TRAVEL., G23007832, G3152186863, NEXT-GENERATION SEQUENCING (NGS) TECHNOLOGIES HAVE RECENTLY BEEN USED TO DETECT AND CLASSIFY EPIGENETIC CHANGES AT AN UNPRECEDENTED LEVEL. EPIGENETIC, Mapping the RNA modification N6-methyladenosine during Zika virus infection, G4198848887, Study of Neural Tube Defects Etiology: Genome and Exposome, G583152162, Joan & Sanford I. Weill Medical College of Cornell University - to monitor the spread of antimicrobial resistance by generating a global map of bacterial species, resistance genes and markers, and modified bases..., G6978605584, G6978705394, Research - Weill Cornell Medical College (2015), G7535378661, G8216312950, G9000278277
OpenAlex ID: W2899573152