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    Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts

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    Type
    Article
    Authors
    Weerdenburg, Eveline M.
    Abdallah, Abdallah
    Rangkuti, Farania
    Abd El Ghany, Moataz
    Otto, Thomas D.
    Adroub, Sabir
    Molenaar, Douwe
    Ummels, Roy
    ter Veen, Kars
    van Stempvoort, Gunny
    van der Sar, Astrid M.
    Ali, Shahjahan
    Langridge, Gemma C.
    Thomson, Nicholas R.
    Pain, Arnab cc
    Bitter, Wilbert cc
    KAUST Department
    Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
    Computer Science Program
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Core Lab
    Bioscience Program
    Pathogen Genomics Laboratory
    Computational Bioscience Research Center (CBRC)
    Date
    2015-02-17
    Online Publication Date
    2015-02-17
    Print Publication Date
    2015-05
    Permanent link to this record
    http://hdl.handle.net/10754/552268
    
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    Abstract
    The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.
    Citation
    Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts 2015, 83 (5):1778 Infection and Immunity
    Publisher
    American Society for Microbiology
    Journal
    Infection and Immunity
    DOI
    10.1128/IAI.03050-14
    PubMed ID
    25690095
    PubMed Central ID
    PMC4399070
    Additional Links
    http://iai.asm.org/lookup/doi/10.1128/IAI.03050-14
    ae974a485f413a2113503eed53cd6c53
    10.1128/IAI.03050-14
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program; Computer Science Program; Computational Bioscience Research Center (CBRC); Bioscience Core Lab; Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division

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