Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Valentin Trofimov, Sébastien Kicka, Sabrina Mucaria, Nabil Hanna, Fernando Ramon-Olayo, Laura Vela-Gonzalez Del Peral, Joël Lelièvre, Lluís Ballell, Leonardo Scapozza, Gurdyal S. Besra, Jonathan A. G. Cox, Thierry Soldati

ABSTRACT

Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK. More... »

PAGES

3939

References to SciGraph publications

  • 2016-12. Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen in SCIENTIFIC REPORTS
  • 2004-03. Interplay between mycobacteria and host signalling pathways in NATURE REVIEWS MICROBIOLOGY
  • 2010-08. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy in NATURE COMMUNICATIONS
  • 2010-09. Evasion of innate immunity by Mycobacterium tuberculosis: is death an exit strategy? in NATURE REVIEWS MICROBIOLOGY
  • 2001-08. Mycobacterium tuberculosis: here today, and here tomorrow in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2013-02-08. Setting Up and Monitoring an Infection of Dictyostelium discoideum with Mycobacteria in DICTYOSTELIUM DISCOIDEUM PROTOCOLS
  • 2013-12. Indoleamides are active against drug-resistant Mycobacterium tuberculosis in NATURE COMMUNICATIONS
  • 2012-08. Nutritional immunity: transition metals at the pathogen–host interface in NATURE REVIEWS MICROBIOLOGY
  • 2008-01. The biology and future prospects of antivirulence therapies in NATURE REVIEWS MICROBIOLOGY
  • 2007-01. Drugs for bad bugs: confronting the challenges of antibacterial discovery in NATURE REVIEWS DRUG DISCOVERY
  • 2012-04. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane in NATURE CHEMICAL BIOLOGY
  • 2010-12. Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis in BMC SYSTEMS BIOLOGY
  • 2016-09-01. Identification of KasA as the cellular target of an anti-tubercular scaffold in NATURE COMMUNICATIONS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-018-22228-6

    DOI

    http://dx.doi.org/10.1038/s41598-018-22228-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1101225843

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29500372


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1108", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical Microbiology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Pasteur Institute of Lille", 
              "id": "https://www.grid.ac/institutes/grid.8970.6", 
              "name": [
                "Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland", 
                "Institut Pasteur de Lille, Lille, France"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Trofimov", 
            "givenName": "Valentin", 
            "id": "sg:person.0714157651.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714157651.01"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Geneva", 
              "id": "https://www.grid.ac/institutes/grid.8591.5", 
              "name": [
                "Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kicka", 
            "givenName": "S\u00e9bastien", 
            "id": "sg:person.0646044451.29", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646044451.29"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Geneva", 
              "id": "https://www.grid.ac/institutes/grid.8591.5", 
              "name": [
                "Pharmaceutical Biochemistry/Chemistry, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Mucaria", 
            "givenName": "Sabrina", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Geneva", 
              "id": "https://www.grid.ac/institutes/grid.8591.5", 
              "name": [
                "Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hanna", 
            "givenName": "Nabil", 
            "id": "sg:person.010715577560.99", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010715577560.99"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "GlaxoSmithKline (Spain)", 
              "id": "https://www.grid.ac/institutes/grid.419327.a", 
              "name": [
                "GSK, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ramon-Olayo", 
            "givenName": "Fernando", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "GlaxoSmithKline (Spain)", 
              "id": "https://www.grid.ac/institutes/grid.419327.a", 
              "name": [
                "GSK, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Del Peral", 
            "givenName": "Laura Vela-Gonzalez", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "GlaxoSmithKline (Spain)", 
              "id": "https://www.grid.ac/institutes/grid.419327.a", 
              "name": [
                "GSK, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Leli\u00e8vre", 
            "givenName": "Jo\u00ebl", 
            "id": "sg:person.0772407262.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0772407262.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "GlaxoSmithKline (Spain)", 
              "id": "https://www.grid.ac/institutes/grid.419327.a", 
              "name": [
                "GSK, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ballell", 
            "givenName": "Llu\u00eds", 
            "id": "sg:person.0703716354.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703716354.28"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Geneva", 
              "id": "https://www.grid.ac/institutes/grid.8591.5", 
              "name": [
                "Pharmaceutical Biochemistry/Chemistry, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Scapozza", 
            "givenName": "Leonardo", 
            "id": "sg:person.0757530434.76", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0757530434.76"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Birmingham", 
              "id": "https://www.grid.ac/institutes/grid.6572.6", 
              "name": [
                "School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Besra", 
            "givenName": "Gurdyal S.", 
            "id": "sg:person.012366545337.89", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012366545337.89"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Aston University", 
              "id": "https://www.grid.ac/institutes/grid.7273.1", 
              "name": [
                "School of Life & Health Sciences, Aston University, Birmingham, UK"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cox", 
            "givenName": "Jonathan A. G.", 
            "id": "sg:person.01010442554.46", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010442554.46"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Geneva", 
              "id": "https://www.grid.ac/institutes/grid.8591.5", 
              "name": [
                "Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Soldati", 
            "givenName": "Thierry", 
            "id": "sg:person.0733226341.50", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733226341.50"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1111/j.1462-5822.2007.01005.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000223046"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acsinfecdis.5b00002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001112929"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/iai.01196-13", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002910373"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/iai.68.2.767-778.2000", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003166883"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2008.11.014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003365334"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd2201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005793977", 
              "https://doi.org/10.1038/nrd2201"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrd2201", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005793977", 
              "https://doi.org/10.1038/nrd2201"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1471-4159.2005.03014.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005934213"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrmicro2836", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010658888", 
              "https://doi.org/10.1038/nrmicro2836"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/aac.00749-08", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013945289"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pbio.0020367", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014535333"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms12581", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015429037", 
              "https://doi.org/10.1038/ncomms12581"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.ppat.1002251", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016006065"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1164/rccm.200904-0536oc", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016509088"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/jb.182.23.6827-6830.2000", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016619916"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-62703-302-2_22", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016931386", 
              "https://doi.org/10.1007/978-1-62703-302-2_22"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-1-62703-302-2_22", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016931386", 
              "https://doi.org/10.1007/978-1-62703-302-2_22"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1590/s0074-02762012000900023", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017898500"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0009823", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018731828"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/emmm.201201772", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023450692"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1462-5822.2009.01413.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024932110"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1462-5822.2009.01413.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024932110"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.mib.2009.11.006", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025970588"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1752-0509-4-160", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026083229", 
              "https://doi.org/10.1186/1752-0509-4-160"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.micpath.2014.07.009", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026729831"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0060143", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1026786578"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0052951", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027694545"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.semcdb.2010.11.003", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029363079"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2217/fmb.12.56", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030300431"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0121492", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030680642"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.coi.2004.05.011", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031329593"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/ec.1.4.643-652.2002", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032004359"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.ppat.1000645", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033372936"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/aac.01920-15", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035330857"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0087834", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035709257"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.ppat.1000895", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035985486"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1084/jem.134.3.713", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036269602"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s1056-8719(00)00107-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036545299"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35085034", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037220032", 
              "https://doi.org/10.1038/35085034"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/35085034", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037220032", 
              "https://doi.org/10.1038/35085034"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrmicro2387", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037228479", 
              "https://doi.org/10.1038/nrmicro2387"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.4049/jimmunol.164.4.2016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037517472"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/cmdc.201200428", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042662402"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms3907", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042891916", 
              "https://doi.org/10.1038/ncomms3907"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.tube.2006.12.001", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043596698"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jac/dks425", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044723557"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0074813", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1044814100"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0010777", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046501025"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jac/dkt155", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047055247"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jac/dkt155", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047055247"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrmicro1818", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1047300775", 
              "https://doi.org/10.1038/nrmicro1818"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms1060", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048093582", 
              "https://doi.org/10.1038/ncomms1060"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ncomms1060", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048093582", 
              "https://doi.org/10.1038/ncomms1060"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/srep38986", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049031647", 
              "https://doi.org/10.1038/srep38986"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2004.11.038", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049070577"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.ejcb.2006.05.010", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049948670"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1462-5822.2007.00993.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049998365"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrmicro840", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050731532", 
              "https://doi.org/10.1038/nrmicro840"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrmicro840", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050731532", 
              "https://doi.org/10.1038/nrmicro840"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nchembio.794", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1050996256", 
              "https://doi.org/10.1038/nchembio.794"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.cell.2010.02.012", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051435618"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/j.1600-0684.2012.00536.x", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051754658"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.ppat.1002093", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051846151"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/j.semcdb.2010.11.006", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053003588"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1242/dmm.016089", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053105038"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/acs.jmedchem.6b00415", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055100121"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/ml200036r", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1056211146"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/cshperspect.a018572", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1060406963"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.1169381", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062459326"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/scitranslmed.3007355", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062688142"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/aac.00826-16", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062709096"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2174/157489108784746579", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1069216816"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2018-12", 
        "datePublishedReg": "2018-12-01", 
        "description": "Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential \"universal\" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/s41598-018-22228-6", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1045337", 
            "issn": [
              "2045-2322"
            ], 
            "name": "Scientific Reports", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "8"
          }
        ], 
        "name": "Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets", 
        "pagination": "3939", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "79b46bb718e50cad8a38db8e49ba482bf5029f27023ef4c3e20362bafb6457f7"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "29500372"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "101563288"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/s41598-018-22228-6"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1101225843"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/s41598-018-22228-6", 
          "https://app.dimensions.ai/details/publication/pub.1101225843"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T10:27", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000349_0000000349/records_113639_00000004.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://www.nature.com/articles/s41598-018-22228-6"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-22228-6'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-22228-6'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-22228-6'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-22228-6'


     

    This table displays all metadata directly associated to this object as RDF triples.

    364 TRIPLES      21 PREDICATES      94 URIs      21 LITERALS      9 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/s41598-018-22228-6 schema:about anzsrc-for:11
    2 anzsrc-for:1108
    3 schema:author Ndb8db348a0194e28b8827f5f566371fe
    4 schema:citation sg:pub.10.1007/978-1-62703-302-2_22
    5 sg:pub.10.1038/35085034
    6 sg:pub.10.1038/nchembio.794
    7 sg:pub.10.1038/ncomms1060
    8 sg:pub.10.1038/ncomms12581
    9 sg:pub.10.1038/ncomms3907
    10 sg:pub.10.1038/nrd2201
    11 sg:pub.10.1038/nrmicro1818
    12 sg:pub.10.1038/nrmicro2387
    13 sg:pub.10.1038/nrmicro2836
    14 sg:pub.10.1038/nrmicro840
    15 sg:pub.10.1038/srep38986
    16 sg:pub.10.1186/1752-0509-4-160
    17 https://doi.org/10.1002/cmdc.201200428
    18 https://doi.org/10.1002/emmm.201201772
    19 https://doi.org/10.1016/j.cell.2004.11.038
    20 https://doi.org/10.1016/j.cell.2008.11.014
    21 https://doi.org/10.1016/j.cell.2010.02.012
    22 https://doi.org/10.1016/j.coi.2004.05.011
    23 https://doi.org/10.1016/j.ejcb.2006.05.010
    24 https://doi.org/10.1016/j.mib.2009.11.006
    25 https://doi.org/10.1016/j.micpath.2014.07.009
    26 https://doi.org/10.1016/j.semcdb.2010.11.003
    27 https://doi.org/10.1016/j.semcdb.2010.11.006
    28 https://doi.org/10.1016/j.tube.2006.12.001
    29 https://doi.org/10.1016/s1056-8719(00)00107-6
    30 https://doi.org/10.1021/acs.jmedchem.6b00415
    31 https://doi.org/10.1021/acsinfecdis.5b00002
    32 https://doi.org/10.1021/ml200036r
    33 https://doi.org/10.1084/jem.134.3.713
    34 https://doi.org/10.1093/jac/dks425
    35 https://doi.org/10.1093/jac/dkt155
    36 https://doi.org/10.1101/cshperspect.a018572
    37 https://doi.org/10.1111/j.1462-5822.2007.00993.x
    38 https://doi.org/10.1111/j.1462-5822.2007.01005.x
    39 https://doi.org/10.1111/j.1462-5822.2009.01413.x
    40 https://doi.org/10.1111/j.1471-4159.2005.03014.x
    41 https://doi.org/10.1111/j.1600-0684.2012.00536.x
    42 https://doi.org/10.1126/science.1169381
    43 https://doi.org/10.1126/scitranslmed.3007355
    44 https://doi.org/10.1128/aac.00749-08
    45 https://doi.org/10.1128/aac.00826-16
    46 https://doi.org/10.1128/aac.01920-15
    47 https://doi.org/10.1128/ec.1.4.643-652.2002
    48 https://doi.org/10.1128/iai.01196-13
    49 https://doi.org/10.1128/iai.68.2.767-778.2000
    50 https://doi.org/10.1128/jb.182.23.6827-6830.2000
    51 https://doi.org/10.1164/rccm.200904-0536oc
    52 https://doi.org/10.1242/dmm.016089
    53 https://doi.org/10.1371/journal.pbio.0020367
    54 https://doi.org/10.1371/journal.pone.0009823
    55 https://doi.org/10.1371/journal.pone.0010777
    56 https://doi.org/10.1371/journal.pone.0052951
    57 https://doi.org/10.1371/journal.pone.0060143
    58 https://doi.org/10.1371/journal.pone.0074813
    59 https://doi.org/10.1371/journal.pone.0087834
    60 https://doi.org/10.1371/journal.pone.0121492
    61 https://doi.org/10.1371/journal.ppat.1000645
    62 https://doi.org/10.1371/journal.ppat.1000895
    63 https://doi.org/10.1371/journal.ppat.1002093
    64 https://doi.org/10.1371/journal.ppat.1002251
    65 https://doi.org/10.1590/s0074-02762012000900023
    66 https://doi.org/10.2174/157489108784746579
    67 https://doi.org/10.2217/fmb.12.56
    68 https://doi.org/10.4049/jimmunol.164.4.2016
    69 schema:datePublished 2018-12
    70 schema:datePublishedReg 2018-12-01
    71 schema:description Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13-14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential "universal" targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.
    72 schema:genre research_article
    73 schema:inLanguage en
    74 schema:isAccessibleForFree true
    75 schema:isPartOf N4e8fd48214ae40b4b4ad6820c6bb9b04
    76 Ne315a899a3fe4629b8672bb06e25d40a
    77 sg:journal.1045337
    78 schema:name Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets
    79 schema:pagination 3939
    80 schema:productId N0c3f348a0fc543ddbcebad3195b4fdc4
    81 N358606104e5d45dfa636dca1604426f4
    82 N78e36363b2a94979aee69d8cb1c6e66f
    83 Nb1ebe3b81dbd4cc997d90884cd70169c
    84 Nba94521dfb7046ed9cf4b828675efc05
    85 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101225843
    86 https://doi.org/10.1038/s41598-018-22228-6
    87 schema:sdDatePublished 2019-04-11T10:27
    88 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    89 schema:sdPublisher N98e9ee4f3bf5412cbac30b0a5d484a52
    90 schema:url https://www.nature.com/articles/s41598-018-22228-6
    91 sgo:license sg:explorer/license/
    92 sgo:sdDataset articles
    93 rdf:type schema:ScholarlyArticle
    94 N0c3f348a0fc543ddbcebad3195b4fdc4 schema:name dimensions_id
    95 schema:value pub.1101225843
    96 rdf:type schema:PropertyValue
    97 N349ad169154040eeb89a4dedd003e3b4 schema:affiliation https://www.grid.ac/institutes/grid.419327.a
    98 schema:familyName Del Peral
    99 schema:givenName Laura Vela-Gonzalez
    100 rdf:type schema:Person
    101 N358606104e5d45dfa636dca1604426f4 schema:name doi
    102 schema:value 10.1038/s41598-018-22228-6
    103 rdf:type schema:PropertyValue
    104 N3706b12cd365487f8d6ddaf1a87eb0f3 rdf:first sg:person.0757530434.76
    105 rdf:rest N57ed62d628d74ca1950bbe7900ca49ac
    106 N3de1de528d83459fa6df5444dde4b13e rdf:first sg:person.010715577560.99
    107 rdf:rest Nbce13699e5d644eeaf4d9966111e7849
    108 N4e8fd48214ae40b4b4ad6820c6bb9b04 schema:issueNumber 1
    109 rdf:type schema:PublicationIssue
    110 N5286e5252f1a4e489dd7a0cb9ab5f8c2 rdf:first sg:person.0772407262.28
    111 rdf:rest N8390a64f9c0449f3b41b30751178f1c7
    112 N57ed62d628d74ca1950bbe7900ca49ac rdf:first sg:person.012366545337.89
    113 rdf:rest Nc668a9fd92eb46a79952605891e815b7
    114 N687e891d15e4404e87b891be4d1a68c6 rdf:first N349ad169154040eeb89a4dedd003e3b4
    115 rdf:rest N5286e5252f1a4e489dd7a0cb9ab5f8c2
    116 N78e36363b2a94979aee69d8cb1c6e66f schema:name nlm_unique_id
    117 schema:value 101563288
    118 rdf:type schema:PropertyValue
    119 N7e5baee32f01469bb14f63f5c23a13ea rdf:first sg:person.0646044451.29
    120 rdf:rest Nfea0ff11fca24ae89d2333930e90e216
    121 N8390a64f9c0449f3b41b30751178f1c7 rdf:first sg:person.0703716354.28
    122 rdf:rest N3706b12cd365487f8d6ddaf1a87eb0f3
    123 N98e9ee4f3bf5412cbac30b0a5d484a52 schema:name Springer Nature - SN SciGraph project
    124 rdf:type schema:Organization
    125 N9a67377d6d5246f1b7ee04ec64572234 schema:affiliation https://www.grid.ac/institutes/grid.419327.a
    126 schema:familyName Ramon-Olayo
    127 schema:givenName Fernando
    128 rdf:type schema:Person
    129 Nb1ebe3b81dbd4cc997d90884cd70169c schema:name readcube_id
    130 schema:value 79b46bb718e50cad8a38db8e49ba482bf5029f27023ef4c3e20362bafb6457f7
    131 rdf:type schema:PropertyValue
    132 Nb956c0d226164e64ae6d7c8922baa085 rdf:first sg:person.0733226341.50
    133 rdf:rest rdf:nil
    134 Nba94521dfb7046ed9cf4b828675efc05 schema:name pubmed_id
    135 schema:value 29500372
    136 rdf:type schema:PropertyValue
    137 Nbce13699e5d644eeaf4d9966111e7849 rdf:first N9a67377d6d5246f1b7ee04ec64572234
    138 rdf:rest N687e891d15e4404e87b891be4d1a68c6
    139 Nc668a9fd92eb46a79952605891e815b7 rdf:first sg:person.01010442554.46
    140 rdf:rest Nb956c0d226164e64ae6d7c8922baa085
    141 Ndb8db348a0194e28b8827f5f566371fe rdf:first sg:person.0714157651.01
    142 rdf:rest N7e5baee32f01469bb14f63f5c23a13ea
    143 Ne315a899a3fe4629b8672bb06e25d40a schema:volumeNumber 8
    144 rdf:type schema:PublicationVolume
    145 Nfb4a1544acb14fa79324fed4ca3c3fe8 schema:affiliation https://www.grid.ac/institutes/grid.8591.5
    146 schema:familyName Mucaria
    147 schema:givenName Sabrina
    148 rdf:type schema:Person
    149 Nfea0ff11fca24ae89d2333930e90e216 rdf:first Nfb4a1544acb14fa79324fed4ca3c3fe8
    150 rdf:rest N3de1de528d83459fa6df5444dde4b13e
    151 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    152 schema:name Medical and Health Sciences
    153 rdf:type schema:DefinedTerm
    154 anzsrc-for:1108 schema:inDefinedTermSet anzsrc-for:
    155 schema:name Medical Microbiology
    156 rdf:type schema:DefinedTerm
    157 sg:journal.1045337 schema:issn 2045-2322
    158 schema:name Scientific Reports
    159 rdf:type schema:Periodical
    160 sg:person.01010442554.46 schema:affiliation https://www.grid.ac/institutes/grid.7273.1
    161 schema:familyName Cox
    162 schema:givenName Jonathan A. G.
    163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01010442554.46
    164 rdf:type schema:Person
    165 sg:person.010715577560.99 schema:affiliation https://www.grid.ac/institutes/grid.8591.5
    166 schema:familyName Hanna
    167 schema:givenName Nabil
    168 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010715577560.99
    169 rdf:type schema:Person
    170 sg:person.012366545337.89 schema:affiliation https://www.grid.ac/institutes/grid.6572.6
    171 schema:familyName Besra
    172 schema:givenName Gurdyal S.
    173 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012366545337.89
    174 rdf:type schema:Person
    175 sg:person.0646044451.29 schema:affiliation https://www.grid.ac/institutes/grid.8591.5
    176 schema:familyName Kicka
    177 schema:givenName Sébastien
    178 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0646044451.29
    179 rdf:type schema:Person
    180 sg:person.0703716354.28 schema:affiliation https://www.grid.ac/institutes/grid.419327.a
    181 schema:familyName Ballell
    182 schema:givenName Lluís
    183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703716354.28
    184 rdf:type schema:Person
    185 sg:person.0714157651.01 schema:affiliation https://www.grid.ac/institutes/grid.8970.6
    186 schema:familyName Trofimov
    187 schema:givenName Valentin
    188 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0714157651.01
    189 rdf:type schema:Person
    190 sg:person.0733226341.50 schema:affiliation https://www.grid.ac/institutes/grid.8591.5
    191 schema:familyName Soldati
    192 schema:givenName Thierry
    193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0733226341.50
    194 rdf:type schema:Person
    195 sg:person.0757530434.76 schema:affiliation https://www.grid.ac/institutes/grid.8591.5
    196 schema:familyName Scapozza
    197 schema:givenName Leonardo
    198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0757530434.76
    199 rdf:type schema:Person
    200 sg:person.0772407262.28 schema:affiliation https://www.grid.ac/institutes/grid.419327.a
    201 schema:familyName Lelièvre
    202 schema:givenName Joël
    203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0772407262.28
    204 rdf:type schema:Person
    205 sg:pub.10.1007/978-1-62703-302-2_22 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016931386
    206 https://doi.org/10.1007/978-1-62703-302-2_22
    207 rdf:type schema:CreativeWork
    208 sg:pub.10.1038/35085034 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037220032
    209 https://doi.org/10.1038/35085034
    210 rdf:type schema:CreativeWork
    211 sg:pub.10.1038/nchembio.794 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050996256
    212 https://doi.org/10.1038/nchembio.794
    213 rdf:type schema:CreativeWork
    214 sg:pub.10.1038/ncomms1060 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048093582
    215 https://doi.org/10.1038/ncomms1060
    216 rdf:type schema:CreativeWork
    217 sg:pub.10.1038/ncomms12581 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015429037
    218 https://doi.org/10.1038/ncomms12581
    219 rdf:type schema:CreativeWork
    220 sg:pub.10.1038/ncomms3907 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042891916
    221 https://doi.org/10.1038/ncomms3907
    222 rdf:type schema:CreativeWork
    223 sg:pub.10.1038/nrd2201 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005793977
    224 https://doi.org/10.1038/nrd2201
    225 rdf:type schema:CreativeWork
    226 sg:pub.10.1038/nrmicro1818 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047300775
    227 https://doi.org/10.1038/nrmicro1818
    228 rdf:type schema:CreativeWork
    229 sg:pub.10.1038/nrmicro2387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037228479
    230 https://doi.org/10.1038/nrmicro2387
    231 rdf:type schema:CreativeWork
    232 sg:pub.10.1038/nrmicro2836 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010658888
    233 https://doi.org/10.1038/nrmicro2836
    234 rdf:type schema:CreativeWork
    235 sg:pub.10.1038/nrmicro840 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050731532
    236 https://doi.org/10.1038/nrmicro840
    237 rdf:type schema:CreativeWork
    238 sg:pub.10.1038/srep38986 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049031647
    239 https://doi.org/10.1038/srep38986
    240 rdf:type schema:CreativeWork
    241 sg:pub.10.1186/1752-0509-4-160 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026083229
    242 https://doi.org/10.1186/1752-0509-4-160
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1002/cmdc.201200428 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042662402
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.1002/emmm.201201772 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023450692
    247 rdf:type schema:CreativeWork
    248 https://doi.org/10.1016/j.cell.2004.11.038 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049070577
    249 rdf:type schema:CreativeWork
    250 https://doi.org/10.1016/j.cell.2008.11.014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003365334
    251 rdf:type schema:CreativeWork
    252 https://doi.org/10.1016/j.cell.2010.02.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051435618
    253 rdf:type schema:CreativeWork
    254 https://doi.org/10.1016/j.coi.2004.05.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031329593
    255 rdf:type schema:CreativeWork
    256 https://doi.org/10.1016/j.ejcb.2006.05.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049948670
    257 rdf:type schema:CreativeWork
    258 https://doi.org/10.1016/j.mib.2009.11.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025970588
    259 rdf:type schema:CreativeWork
    260 https://doi.org/10.1016/j.micpath.2014.07.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026729831
    261 rdf:type schema:CreativeWork
    262 https://doi.org/10.1016/j.semcdb.2010.11.003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029363079
    263 rdf:type schema:CreativeWork
    264 https://doi.org/10.1016/j.semcdb.2010.11.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053003588
    265 rdf:type schema:CreativeWork
    266 https://doi.org/10.1016/j.tube.2006.12.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043596698
    267 rdf:type schema:CreativeWork
    268 https://doi.org/10.1016/s1056-8719(00)00107-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036545299
    269 rdf:type schema:CreativeWork
    270 https://doi.org/10.1021/acs.jmedchem.6b00415 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055100121
    271 rdf:type schema:CreativeWork
    272 https://doi.org/10.1021/acsinfecdis.5b00002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001112929
    273 rdf:type schema:CreativeWork
    274 https://doi.org/10.1021/ml200036r schema:sameAs https://app.dimensions.ai/details/publication/pub.1056211146
    275 rdf:type schema:CreativeWork
    276 https://doi.org/10.1084/jem.134.3.713 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036269602
    277 rdf:type schema:CreativeWork
    278 https://doi.org/10.1093/jac/dks425 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044723557
    279 rdf:type schema:CreativeWork
    280 https://doi.org/10.1093/jac/dkt155 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047055247
    281 rdf:type schema:CreativeWork
    282 https://doi.org/10.1101/cshperspect.a018572 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060406963
    283 rdf:type schema:CreativeWork
    284 https://doi.org/10.1111/j.1462-5822.2007.00993.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1049998365
    285 rdf:type schema:CreativeWork
    286 https://doi.org/10.1111/j.1462-5822.2007.01005.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1000223046
    287 rdf:type schema:CreativeWork
    288 https://doi.org/10.1111/j.1462-5822.2009.01413.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1024932110
    289 rdf:type schema:CreativeWork
    290 https://doi.org/10.1111/j.1471-4159.2005.03014.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1005934213
    291 rdf:type schema:CreativeWork
    292 https://doi.org/10.1111/j.1600-0684.2012.00536.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1051754658
    293 rdf:type schema:CreativeWork
    294 https://doi.org/10.1126/science.1169381 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062459326
    295 rdf:type schema:CreativeWork
    296 https://doi.org/10.1126/scitranslmed.3007355 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062688142
    297 rdf:type schema:CreativeWork
    298 https://doi.org/10.1128/aac.00749-08 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013945289
    299 rdf:type schema:CreativeWork
    300 https://doi.org/10.1128/aac.00826-16 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062709096
    301 rdf:type schema:CreativeWork
    302 https://doi.org/10.1128/aac.01920-15 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035330857
    303 rdf:type schema:CreativeWork
    304 https://doi.org/10.1128/ec.1.4.643-652.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032004359
    305 rdf:type schema:CreativeWork
    306 https://doi.org/10.1128/iai.01196-13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002910373
    307 rdf:type schema:CreativeWork
    308 https://doi.org/10.1128/iai.68.2.767-778.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003166883
    309 rdf:type schema:CreativeWork
    310 https://doi.org/10.1128/jb.182.23.6827-6830.2000 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016619916
    311 rdf:type schema:CreativeWork
    312 https://doi.org/10.1164/rccm.200904-0536oc schema:sameAs https://app.dimensions.ai/details/publication/pub.1016509088
    313 rdf:type schema:CreativeWork
    314 https://doi.org/10.1242/dmm.016089 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053105038
    315 rdf:type schema:CreativeWork
    316 https://doi.org/10.1371/journal.pbio.0020367 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014535333
    317 rdf:type schema:CreativeWork
    318 https://doi.org/10.1371/journal.pone.0009823 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018731828
    319 rdf:type schema:CreativeWork
    320 https://doi.org/10.1371/journal.pone.0010777 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046501025
    321 rdf:type schema:CreativeWork
    322 https://doi.org/10.1371/journal.pone.0052951 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027694545
    323 rdf:type schema:CreativeWork
    324 https://doi.org/10.1371/journal.pone.0060143 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026786578
    325 rdf:type schema:CreativeWork
    326 https://doi.org/10.1371/journal.pone.0074813 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044814100
    327 rdf:type schema:CreativeWork
    328 https://doi.org/10.1371/journal.pone.0087834 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035709257
    329 rdf:type schema:CreativeWork
    330 https://doi.org/10.1371/journal.pone.0121492 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030680642
    331 rdf:type schema:CreativeWork
    332 https://doi.org/10.1371/journal.ppat.1000645 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033372936
    333 rdf:type schema:CreativeWork
    334 https://doi.org/10.1371/journal.ppat.1000895 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035985486
    335 rdf:type schema:CreativeWork
    336 https://doi.org/10.1371/journal.ppat.1002093 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051846151
    337 rdf:type schema:CreativeWork
    338 https://doi.org/10.1371/journal.ppat.1002251 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016006065
    339 rdf:type schema:CreativeWork
    340 https://doi.org/10.1590/s0074-02762012000900023 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017898500
    341 rdf:type schema:CreativeWork
    342 https://doi.org/10.2174/157489108784746579 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069216816
    343 rdf:type schema:CreativeWork
    344 https://doi.org/10.2217/fmb.12.56 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030300431
    345 rdf:type schema:CreativeWork
    346 https://doi.org/10.4049/jimmunol.164.4.2016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037517472
    347 rdf:type schema:CreativeWork
    348 https://www.grid.ac/institutes/grid.419327.a schema:alternateName GlaxoSmithKline (Spain)
    349 schema:name GSK, Severo Ochoa 2, 28760 Tres Cantos, Madrid, Spain
    350 rdf:type schema:Organization
    351 https://www.grid.ac/institutes/grid.6572.6 schema:alternateName University of Birmingham
    352 schema:name School of Biosciences, University of Birmingham, Edgbaston, Birmingham, UK
    353 rdf:type schema:Organization
    354 https://www.grid.ac/institutes/grid.7273.1 schema:alternateName Aston University
    355 schema:name School of Life & Health Sciences, Aston University, Birmingham, UK
    356 rdf:type schema:Organization
    357 https://www.grid.ac/institutes/grid.8591.5 schema:alternateName University of Geneva
    358 schema:name Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland
    359 Pharmaceutical Biochemistry/Chemistry, School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
    360 rdf:type schema:Organization
    361 https://www.grid.ac/institutes/grid.8970.6 schema:alternateName Pasteur Institute of Lille
    362 schema:name Department of Biochemistry, Faculty of Science, University of Geneva, Geneva, Switzerland
    363 Institut Pasteur de Lille, Lille, France
    364 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...