More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells
The genus comprises 65 species, among which is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encodin...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS Jg. 116; H. 6; S. 2265 |
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05.02.2019
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| Abstract | The genus
comprises 65 species, among which
is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80
genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and
Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to
and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens. |
|---|---|
| AbstractList | The genus
comprises 65 species, among which
is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80
genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and
Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to
and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens. The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 Legionella genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and Legionella Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to L. pneumophila and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens.The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 Legionella genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and Legionella Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to L. pneumophila and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens. |
| Author | Demirtas, Jasmin Rusniok, Christophe Pasricha, Shivani Pérez-Cobas, Ana Elena Crumbach, Johannes Mondino, Sonia Dougan, Gordon Carson, Danielle Schroeder, Gunnar N Rolando, Monica Buchrieser, Carmen Reuter, Sandra Jarraud, Sophie Hartland, Elizabeth L Gomez-Valero, Laura Descorps-Declere, Stephane Frankel, Gad |
| Author_xml | – sequence: 1 givenname: Laura surname: Gomez-Valero fullname: Gomez-Valero, Laura email: lgomez@pasteur.fr, cbuch@pasteur.fr organization: CNRS UMR 3525, 75724 Paris, France – sequence: 2 givenname: Christophe surname: Rusniok fullname: Rusniok, Christophe organization: CNRS UMR 3525, 75724 Paris, France – sequence: 3 givenname: Danielle surname: Carson fullname: Carson, Danielle organization: Medical Research Council Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom – sequence: 4 givenname: Sonia surname: Mondino fullname: Mondino, Sonia organization: CNRS UMR 3525, 75724 Paris, France – sequence: 5 givenname: Ana Elena surname: Pérez-Cobas fullname: Pérez-Cobas, Ana Elena organization: CNRS UMR 3525, 75724 Paris, France – sequence: 6 givenname: Monica orcidid: 0000-0002-3710-0115 surname: Rolando fullname: Rolando, Monica organization: CNRS UMR 3525, 75724 Paris, France – sequence: 7 givenname: Shivani surname: Pasricha fullname: Pasricha, Shivani organization: Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia – sequence: 8 givenname: Sandra surname: Reuter fullname: Reuter, Sandra organization: Pathogen Genomics, Wellcome Trust Sanger Institute, CB10 1SA Cambridge, United Kingdom – sequence: 9 givenname: Jasmin surname: Demirtas fullname: Demirtas, Jasmin organization: CNRS UMR 3525, 75724 Paris, France – sequence: 10 givenname: Johannes surname: Crumbach fullname: Crumbach, Johannes organization: CNRS UMR 3525, 75724 Paris, France – sequence: 11 givenname: Stephane surname: Descorps-Declere fullname: Descorps-Declere, Stephane organization: Institut Pasteur, Center of Bioinformatics, Biostatistics and Integrative Biology, 75724 Paris, France – sequence: 12 givenname: Elizabeth L surname: Hartland fullname: Hartland, Elizabeth L organization: Department of Molecular and Translational Science, Monash University, Clayton, VIC 3168, Australia – sequence: 13 givenname: Sophie surname: Jarraud fullname: Jarraud, Sophie organization: National Reference Centre of Legionella, Hospices Civils de Lyon, 69317 Lyon, France – sequence: 14 givenname: Gordon surname: Dougan fullname: Dougan, Gordon organization: Pathogen Genomics, Wellcome Trust Sanger Institute, CB10 1SA Cambridge, United Kingdom – sequence: 15 givenname: Gunnar N surname: Schroeder fullname: Schroeder, Gunnar N organization: Centre for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, United Kingdom – sequence: 16 givenname: Gad surname: Frankel fullname: Frankel, Gad organization: Medical Research Council Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom – sequence: 17 givenname: Carmen surname: Buchrieser fullname: Buchrieser, Carmen email: lgomez@pasteur.fr, cbuch@pasteur.fr organization: CNRS UMR 3525, 75724 Paris, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30659146$$D View this record in MEDLINE/PubMed |
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| Snippet | The genus
comprises 65 species, among which
is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental... The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an... |
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| SubjectTerms | Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Secretion Systems - genetics Computational Biology - methods Evolution, Molecular Genome, Bacterial Genomics - methods Humans Intracellular Space - microbiology Legionella - classification Legionella - physiology Legionellosis - microbiology Phylogeny Protein Domains |
| Title | More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells |
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