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

Handle URI:
http://hdl.handle.net/10754/552268
Title:
Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts
Authors:
Weerdenburg, Eveline M.; Abdallah, Abdallah; Rangkuti, Farania; Abd El Ghany, Moataz; Otto, Thomas D.; Adroub, Sabir A.; 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 ( 0000-0002-1755-2819 ) ; Bitter, Wilbert
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.
KAUST Department:
Pathogen Genomics Laboratory; Computational Bioscience Research Center (CBRC); Biosciences Core Lab
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
Journal:
Infection and Immunity
Issue Date:
17-Feb-2015
DOI:
10.1128/IAI.03050-14
PubMed ID:
25690095
PubMed Central ID:
PMC4399070
Type:
Article
ISSN:
0019-9567; 1098-5522
Additional Links:
http://iai.asm.org/lookup/doi/10.1128/IAI.03050-14
Appears in Collections:
Articles; Biosciences Core Lab; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorWeerdenburg, Eveline M.en
dc.contributor.authorAbdallah, Abdallahen
dc.contributor.authorRangkuti, Faraniaen
dc.contributor.authorAbd El Ghany, Moatazen
dc.contributor.authorOtto, Thomas D.en
dc.contributor.authorAdroub, Sabir A.en
dc.contributor.authorMolenaar, Douween
dc.contributor.authorUmmels, Royen
dc.contributor.authorter Veen, Karsen
dc.contributor.authorvan Stempvoort, Gunnyen
dc.contributor.authorvan der Sar, Astrid M.en
dc.contributor.authorAli, Shahjahanen
dc.contributor.authorLangridge, Gemma C.en
dc.contributor.authorThomson, Nicholas R.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorBitter, Wilberten
dc.date.accessioned2015-05-05T08:49:52Zen
dc.date.available2015-05-05T08:49:52Zen
dc.date.issued2015-02-17en
dc.identifier.citationGenome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts 2015, 83 (5):1778 Infection and Immunityen
dc.identifier.issn0019-9567en
dc.identifier.issn1098-5522en
dc.identifier.pmid25690095en
dc.identifier.doi10.1128/IAI.03050-14en
dc.identifier.urihttp://hdl.handle.net/10754/552268en
dc.description.abstractThe 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.en
dc.relation.urlhttp://iai.asm.org/lookup/doi/10.1128/IAI.03050-14en
dc.rightsArchived with thanks to Infection and Immunityen
dc.titleGenome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hostsen
dc.typeArticleen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentBiosciences Core Laben
dc.identifier.journalInfection and Immunityen
dc.identifier.pmcidPMC4399070en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDepartment of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlandsen
kaust.authorRangkuti, Farania Gama Ardhinaen
kaust.authorAbd El Ghany, Moatazen
kaust.authorAdroub, Sabiren
kaust.authorAli, Shahjahanen
kaust.authorPain, Arnaben
kaust.authorAbdallah, Abdallahen

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