Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.

E.M. Weerdenburg, A. Abdallah, F. Rangkuti, M. Abd El Ghany, T.D. Otto, S.A. Adroub, D. Molenaar, R. Ummels, K. Ter Veen, G. van Stempvoort, A.M. van der Sar, S. Ali, G.C. Langridge, N.R. Thomson, A. Pain, W. Bitter

Research output: Contribution to JournalArticleAcademicpeer-review

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.
Original languageEnglish
Article number5
Pages (from-to)1778-1788
JournalInfection and Immunity
Issue number83
DOIs
Publication statusPublished - 2015

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Mycobacterium marinum
Mutagenesis
Virulence
Genome
Phagocytes
Vertebrates
Polyketides
Amoeba
Glycolipids
Virulence Factors
Sterols
Eukaryota
Proteins
Bacteria
Lipids

Cite this

Weerdenburg, E.M. ; Abdallah, A. ; Rangkuti, F. ; Abd El Ghany, M. ; Otto, T.D. ; Adroub, S.A. ; Molenaar, D. ; Ummels, R. ; Ter Veen, K. ; van Stempvoort, G. ; van der Sar, A.M. ; Ali, S. ; Langridge, G.C. ; Thomson, N.R. ; Pain, A. ; Bitter, W. / Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts. In: Infection and Immunity. 2015 ; No. 83. pp. 1778-1788.
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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.",
author = "E.M. Weerdenburg and A. Abdallah and F. Rangkuti and {Abd El Ghany}, M. and T.D. Otto and S.A. Adroub and D. Molenaar and R. Ummels and {Ter Veen}, K. and {van Stempvoort}, G. and {van der Sar}, A.M. and S. Ali and G.C. Langridge and N.R. Thomson and A. Pain and W. Bitter",
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Weerdenburg, EM, Abdallah, A, Rangkuti, F, Abd El Ghany, M, Otto, TD, Adroub, SA, Molenaar, D, Ummels, R, Ter Veen, K, van Stempvoort, G, van der Sar, AM, Ali, S, Langridge, GC, Thomson, NR, Pain, A & Bitter, W 2015, 'Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.' Infection and Immunity, no. 83, 5, pp. 1778-1788. https://doi.org/10.1128/IAI.03050-14

Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts. / Weerdenburg, E.M.; Abdallah, A.; Rangkuti, F.; Abd El Ghany, M.; Otto, T.D.; Adroub, S.A.; Molenaar, D.; Ummels, R.; Ter Veen, K.; van Stempvoort, G.; van der Sar, A.M.; Ali, S.; Langridge, G.C.; Thomson, N.R.; Pain, A.; Bitter, W.

In: Infection and Immunity, No. 83, 5, 2015, p. 1778-1788.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Genome-wide transposon mutagenesis indicates that Mycobacterium marinum customizes its virulence mechanisms for survival and replication in different hosts.

AU - Weerdenburg, E.M.

AU - Abdallah, A.

AU - Rangkuti, F.

AU - Abd El Ghany, M.

AU - Otto, T.D.

AU - Adroub, S.A.

AU - Molenaar, D.

AU - Ummels, R.

AU - Ter Veen, K.

AU - van Stempvoort, G.

AU - van der Sar, A.M.

AU - Ali, S.

AU - Langridge, G.C.

AU - Thomson, N.R.

AU - Pain, A.

AU - Bitter, W.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1128/IAI.03050-14

DO - 10.1128/IAI.03050-14

M3 - Article

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EP - 1788

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

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