More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells
| Autor: | Gordon Dougan, Ana Elena Pérez-Cobas, Christophe Rusniok, Sandra Reuter, Carmen Buchrieser, Jasmin Demirtas, Shivani Pasricha, Elizabeth L. Hartland, Gunnar N. Schroeder, Gad Frankel, S. Jarraud, Sonia Mondino, Laura Gomez-Valero, Johannes Crumbach, Monica Rolando, Stéphane Descorps-Declère, Danielle Carson |
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| Přispěvatelé: | Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Medical Research Council Centre for Molecular Bacteriology and Infection [Londres, Royaume-Uni] (MRC CMBI), Imperial College London, Department of Life Sciences, The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, The Wellcome Trust Sanger Institute [Cambridge], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Monash University [Clayton], Centre for Innate Immunity and Infectious Diseases [Clayton] (CiiiD), Hudson Institute of Medical Research [Clayton], Centre National de Référence des Légionelles (CNR), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wellcome-Wolfson Institute For Experimental Medicine [Belfast] (WWIEM), School of Medicine, Dentistry and Biomedical Sciences [Belfast], Queen's University [Belfast] (QUB)-Queen's University [Belfast] (QUB), Work in the C.B. laboratory is financed by the Institut Pasteur, the Agence Nationale de la Recherche Grant ANR-10-LABX-62-IBEID, and the Fondation pour la Recherche Médicale Grant DEQ20120323697., We thank Tim P. Stinear for critical reading of the manuscript and helpful comments, and we acknowledge the receipt of 53 different Legionella strains from the Collection of the Institut Pasteur., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rolando, Monica [0000-0002-3710-0115], Apollo - University of Cambridge Repository, HOFFMANN, Isabelle, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Intracellular Space
MESH: Intracellular Space/microbiology co-evolution Legionella pneumophila Genome protozoa human pathogen MESH: Computational Biology/methods MESH: Bacterial Secretion Systems/genetics MESH: Phylogeny Bacterial Secretion Systems Phylogeny virulence 29 30 MESH: Evolution Molecular Genetics 0303 health sciences Multidisciplinary biology Effector Genomics Phenotype MESH: Genomics/methods Horizontal gene transfer coevolution [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] horizontal gene transfer MESH: Protein Domains MESH: Bacterial Proteins/chemistry Legionella Protein domain MESH: Bacterial Proteins/genetics Evolution Molecular 03 medical and health sciences Bacterial Proteins Protein Domains [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Humans Gene MESH: Legionella/classification 030304 developmental biology Legionellosis MESH: Humans 030306 microbiology Computational Biology MESH: Genome Bacterial biology.organism_classification MESH: Legionellosis/microbiology MESH: Legionella/physiology Genome Bacterial |
| Zdroj: | Gomez-Valero, L, Rusniok, C, Carson, D, Mondino, S, Pérez-Cobas, A E, Rolando, M, Pasricha, S, Reuter, S, Demirtas, J, Crumbach, J, Descorps-Declere, S, Hartland, E L, Jarraud, S, Dougan, G, Schroeder, G N, Frankel, G & Buchrieser, C 2019, ' More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells ', Proceedings of the National Academy of Sciences of the United States of America . https://doi.org/10.1073/pnas.1808016116, https://doi.org/10.1101/350777 Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2019, 116 (6), pp.2265-2273. ⟨10.1073/pnas.1808016116⟩ Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (6), pp.2265-2273. ⟨10.1073/pnas.1808016116⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.1808016116 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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