title: Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.
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.
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eveline M
authors.initials: EM
authors.lastname: Weerdenburg
authors.affiliation: Pathogen Genomics Laboratory, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia.
authors.forename: Abdallah M
authors.initials: AM
authors.lastname: Abdallah
authors.affiliation: Pathogen Genomics Laboratory, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia.
authors.forename: Farania
authors.initials: F
authors.lastname: Rangkuti
authors.affiliation: Pathogen Genomics Laboratory, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia.
authors.forename: Moataz
authors.initials: M
authors.lastname: Abd El Ghany
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.affiliation: Pathogen Genomics Laboratory, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia.
authors.forename: Sabir A
authors.initials: SA
authors.lastname: Adroub
authors.affiliation: Systems Bioinformatics/Center for Integrative Bioinformatics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: Douwe
authors.initials: D
authors.lastname: Molenaar
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Ummels
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Kars
authors.initials: K
authors.lastname: Ter Veen
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gunny
authors.initials: G
authors.lastname: van Stempvoort
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: van der Sar
authors.affiliation: Bioscience Core Laboratory, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia.
authors.forename: Shahjahan
authors.initials: S
authors.lastname: Ali
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Langridge
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: Pathogen Genomics Laboratory, Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal-Jeddah, Kingdom of Saudi Arabia arnab.pain@kaust.edu.sa w.bitter@vumc.nl.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands arnab.pain@kaust.edu.sa w.bitter@vumc.nl.
authors.forename: Wilbert
authors.initials: W
authors.lastname: Bitter
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology; D000818:Animals; D004251:DNA Transposable Elements; D004023:Dictyostelium / Q000382:microbiology; D016680:Genome, Bacterial; D006801:Humans; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D019910:Mycobacterium marinum / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D010586:Phagocytes / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D037521:Virulence Factors