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...
Saved in:
| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 6; p. 2265 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
05.02.2019
|
| Subjects: | |
| ISSN: | 1091-6490, 1091-6490 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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 |
| BookMark | eNpNUDtPwzAQtlARpYWZDXlkaIsf8SMjqnhJRSwwR45zbo0SJ8QJEjN_HBeKxHJ3uvteuhmahDYAQheUrChR_LoLJq6oJppQSak8QqeU5HQps5xM_s1TNIvxjRCSC01O0JQTKXKayVP09dT2gIedCZjqRUJgcA7s0PYR-5AOgDew9cm1rg3eQhjjvrYN4K5vP3wFuBnrwXc1LBKhgg5SCQO2bVP6YIZEjdi1Pe6hq739WeyVd2OTPG2SjWfo2Jk6wvmhz9Hr3e3L-mG5eb5_XN9sllZQNSxLUSotFSu1EbwsXZlXhoIBbYlQrlI2s1LxXHIBhjnmaEUsY5zzilCwJGdzdPWrm5K_jxCHovFxn8AEaMdYMKpyrgXLdIJeHqBj2UBVdL1vTP9Z_D2OfQOLgnO6 |
| CitedBy_id | crossref_primary_10_1093_jacamr_dlac040 crossref_primary_10_2478_ahem_2021_0034 crossref_primary_10_1186_s13613_024_01252_y crossref_primary_10_3389_fcimb_2021_708228 crossref_primary_10_1038_s41564_019_0663_7 crossref_primary_10_1016_j_bbalip_2022_159138 crossref_primary_10_1038_s41467_021_23777_7 crossref_primary_10_7717_peerj_12000 crossref_primary_10_1128_iai_00072_23 crossref_primary_10_1371_journal_pone_0281587 crossref_primary_10_1016_j_mimet_2021_106242 crossref_primary_10_1111_1348_0421_12951 crossref_primary_10_1128_msystems_01004_24 crossref_primary_10_1371_journal_ppat_1012118 crossref_primary_10_1093_molbev_msaf161 crossref_primary_10_1128_iai_00441_22 crossref_primary_10_1093_molbev_msac037 crossref_primary_10_1007_s10123_021_00192_y crossref_primary_10_1002_pro_4889 crossref_primary_10_1146_annurev_pathmechdis_012419_032742 crossref_primary_10_1038_s41467_024_54649_5 crossref_primary_10_1111_mmi_14770 crossref_primary_10_1128_msphere_00354_24 crossref_primary_10_3389_fcimb_2021_608860 crossref_primary_10_1038_s41467_020_15123_0 crossref_primary_10_1128_mbio_01268_25 crossref_primary_10_1186_s40168_024_01809_w crossref_primary_10_1128_msphere_00552_22 crossref_primary_10_1111_febs_15794 crossref_primary_10_1042_BST20190712 crossref_primary_10_3390_microorganisms11010074 crossref_primary_10_1093_femsre_fuae021 crossref_primary_10_1107_S2059798321010469 crossref_primary_10_1038_s41467_022_28454_x crossref_primary_10_1146_annurev_genet_111523_102030 crossref_primary_10_7717_peerj_17197 crossref_primary_10_1093_femspd_ftz065 crossref_primary_10_1111_mmi_15172 crossref_primary_10_1038_s41467_024_51273_1 crossref_primary_10_1111_mmi_15214 crossref_primary_10_1016_j_jbc_2021_101340 crossref_primary_10_1111_mmi_14760 crossref_primary_10_1073_pnas_2303942120 crossref_primary_10_3389_frwa_2022_891477 crossref_primary_10_1016_j_tim_2020_05_020 crossref_primary_10_1186_s40168_020_00926_6 crossref_primary_10_3389_fcimb_2020_599762 crossref_primary_10_1107_S2059798322007318 crossref_primary_10_1016_j_tim_2023_05_011 crossref_primary_10_1093_femsre_fuad040 crossref_primary_10_1099_mgen_0_000407 crossref_primary_10_1128_msphere_00891_24 crossref_primary_10_1128_Spectrum_00424_21 crossref_primary_10_1128_jb_00324_24 crossref_primary_10_1038_s41598_022_26109_x crossref_primary_10_1093_bioinformatics_btaf398 crossref_primary_10_1038_s41467_021_27478_z crossref_primary_10_15252_embr_202051163 crossref_primary_10_1099_ijsem_0_006813 crossref_primary_10_1111_cmi_13246 crossref_primary_10_1038_s41579_023_00974_3 crossref_primary_10_1111_mmi_15201 crossref_primary_10_1093_femsml_uqac014 crossref_primary_10_1128_IAI_00261_21 crossref_primary_10_1128_microbiolspec_PSIB_0027_2019 crossref_primary_10_1038_s41467_023_37885_z crossref_primary_10_1016_j_tim_2020_09_012 crossref_primary_10_3390_microorganisms9020291 crossref_primary_10_1093_nar_gkaf652 crossref_primary_10_1016_j_jbc_2021_100301 crossref_primary_10_1038_s42003_021_01672_7 crossref_primary_10_1371_journal_ppat_1011473 crossref_primary_10_3389_fmicb_2021_695346 crossref_primary_10_1038_s41579_019_0155_z crossref_primary_10_1128_msphere_01002_24 crossref_primary_10_1016_j_micinf_2019_06_012 crossref_primary_10_1038_s41396_023_01502_0 crossref_primary_10_1038_s41467_024_51272_2 crossref_primary_10_7717_peerj_7346 crossref_primary_10_3390_biom11121802 crossref_primary_10_1016_j_mib_2020_04_002 crossref_primary_10_1016_j_ijheh_2023_114117 crossref_primary_10_1371_journal_pone_0223033 crossref_primary_10_1128_IAI_00374_19 crossref_primary_10_1016_j_mib_2019_12_004 crossref_primary_10_1016_j_plaphy_2024_109411 crossref_primary_10_1007_s00018_025_05610_2 crossref_primary_10_3390_jcm11206126 crossref_primary_10_1093_femsre_fuac012 crossref_primary_10_1016_j_tim_2023_03_005 crossref_primary_10_7554_eLife_86903 crossref_primary_10_3390_membranes13030356 crossref_primary_10_24072_pcjournal_269 crossref_primary_10_1093_g3journal_jkae158 crossref_primary_10_1128_IAI_00153_19 crossref_primary_10_1111_cmi_13384 crossref_primary_10_1093_infdis_jiz340 crossref_primary_10_1038_s41467_019_13021_8 crossref_primary_10_1128_msphere_00454_22 crossref_primary_10_1111_febs_15627 crossref_primary_10_1093_femsle_fnad086 crossref_primary_10_1099_mgen_0_000273 crossref_primary_10_1016_j_heliyon_2019_e03149 crossref_primary_10_3389_fimmu_2020_00025 crossref_primary_10_1016_j_tim_2020_01_005 crossref_primary_10_1038_s44320_024_00076_z crossref_primary_10_1128_spectrum_04179_22 crossref_primary_10_1007_s12275_024_00162_9 crossref_primary_10_1093_femsml_uqab013 crossref_primary_10_1111_1758_2229_70132 crossref_primary_10_1080_15548627_2022_2025572 crossref_primary_10_1038_s41467_020_16681_z crossref_primary_10_3389_fcimb_2023_1140688 crossref_primary_10_3389_fmicb_2023_1113021 crossref_primary_10_1093_femsre_fuaf022 crossref_primary_10_1371_journal_ppat_1012534 crossref_primary_10_1128_mmbr_00097_23 crossref_primary_10_1099_mic_0_001551 crossref_primary_10_3389_fmicb_2021_613067 crossref_primary_10_3390_microorganisms9010174 crossref_primary_10_1128_MRA_01276_20 crossref_primary_10_3390_microorganisms10020255 crossref_primary_10_1038_s41435_019_0074_z crossref_primary_10_1128_msphere_00352_25 crossref_primary_10_1128_msphere_00222_24 crossref_primary_10_1038_s41598_022_09721_9 crossref_primary_10_1371_journal_ppat_1012010 crossref_primary_10_7554_eLife_86903_3 crossref_primary_10_1111_tra_12860 crossref_primary_10_1016_j_mib_2020_01_008 crossref_primary_10_3390_toxins12040220 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1073/pnas.1808016116 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Sciences (General) |
| EISSN | 1091-6490 |
| ExternalDocumentID | 30659146 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: Medical Research Council grantid: MR/P028225/1 – fundername: Medical Research Council grantid: G1001729 – fundername: Medical Research Council grantid: MR/L018225/1 |
| GroupedDBID | --- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACHIC ACIWK ACNCT ACPRK ADQXQ ADULT AENEX AEUPB AEXZC AFFNX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AQVQM BKOMP CGR CS3 CUY CVF D0L DCCCD DIK DU5 E3Z EBS ECM EIF EJD F5P FRP GX1 H13 HH5 HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 N9A NPM N~3 O9- OK1 PNE PQQKQ R.V RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM 7X8 |
| ID | FETCH-LOGICAL-c517t-b5b78672b8a53bbfb9da1eae8c057fd7c4c6739635ea2f2f1d0c22333d01ec092 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 158 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000457731900071&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1091-6490 |
| IngestDate | Fri Sep 05 09:35:46 EDT 2025 Sat May 31 02:14:06 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Keywords | Legionella human pathogen horizontal gene transfer coevolution protozoa |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c517t-b5b78672b8a53bbfb9da1eae8c057fd7c4c6739635ea2f2f1d0c22333d01ec092 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0002-3710-0115 |
| OpenAccessLink | https://pasteur.hal.science/pasteur-02563435 |
| PMID | 30659146 |
| PQID | 2179385248 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2179385248 pubmed_primary_30659146 |
| PublicationCentury | 2000 |
| PublicationDate | 2019-02-05 |
| PublicationDateYYYYMMDD | 2019-02-05 |
| PublicationDate_xml | – month: 02 year: 2019 text: 2019-02-05 day: 05 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Proceedings of the National Academy of Sciences - PNAS |
| PublicationTitleAlternate | Proc Natl Acad Sci U S A |
| PublicationYear | 2019 |
| SSID | ssj0009580 |
| Score | 2.6342247 |
| 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... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 2265 |
| 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 |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/30659146 https://www.proquest.com/docview/2179385248 |
| Volume | 116 |
| WOSCitedRecordID | wos000457731900071&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV07T8MwELaAMrAA5VleMhIDSJjWzsPOhBCiYmirDiB1q_yK1IGkNC1_gD_OXZIWFiQkFi9RrIt9d_l89_mOkCuleQqowjE4T0csNEIyHTvJ8DoCN1I7Ycud7snBQI1GybAOuBU1rXLpE0tH7XKLMfK2QE1SkQjV_fSdYdcozK7WLTTWSSMAKIOULjlSP4ruqqoaQcJZHCadZWkfGbSnmS7uOBZVBMjD49_xZfmf6e78V8Jdsl0jTPpQqUSTrPlsjzRrGy7odV1o-maffPbzmacYO6dc3cKX0Irdkc8KOsnggac9j3xlZEhR0LRFgWP-5ml9gY8u-Yi3dLLqpzunIC8cuKtYIAVUTGd-lSbHmcvGgBRzBsUBee0-vTw-s7opA7MRl3NmIiNVLIVROgqMSU3iNPfaKwvIL3XShjaWAZh15LVIRcpdxwIECQLX4d52EnFINjIQ_JhQm2KTYaHBxyQhHAyNxYhsYEIcU-la5HK50GNQepRKZz5fFOPvpW6Ro2q3xtOqOsc4wEwx-P-TP7x9SrYAACUlCzs6I40UTN6fk037MZ8Us4tSm2AcDPtfByPVXA |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=More+than+18%2C000+effectors+in+the+Legionella+genus+genome+provide+multiple%2C+independent+combinations+for+replication+in+human+cells&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Gomez-Valero%2C+Laura&rft.au=Rusniok%2C+Christophe&rft.au=Carson%2C+Danielle&rft.au=Mondino%2C+Sonia&rft.date=2019-02-05&rft.eissn=1091-6490&rft.volume=116&rft.issue=6&rft.spage=2265&rft_id=info:doi/10.1073%2Fpnas.1808016116&rft_id=info%3Apmid%2F30659146&rft_id=info%3Apmid%2F30659146&rft.externalDocID=30659146 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1091-6490&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1091-6490&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1091-6490&client=summon |