{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T21:50:46Z","timestamp":1776721846529,"version":"3.51.2"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A first strong evidence of person-to-person transmission of Legionnaires\u2019 Disease (LD) was recently reported. Here, we characterize the genetic backbone of this case-related <jats:italic>Legionella pneumophila<\/jats:italic> strain (\u201cPtVFX\/2014\u201d), which also caused a large outbreak of LD. PtVFX\/2014 is phylogenetically divergent from the most worldwide studied outbreak-associated <jats:italic>L. pneumophila<\/jats:italic> subspecies <jats:italic>pneumophila<\/jats:italic> serogroup 1 strains. In fact, this strain is also from serogroup 1, but belongs to the <jats:italic>L. pneumophila<\/jats:italic> subspecies <jats:italic>fraseri<\/jats:italic>. Its genomic mosaic backbone reveals eight horizontally transferred regions encompassing genes, for instance, involved in lipopolysaccharide biosynthesis or encoding virulence-associated Dot\/Icm type IVB secretion system (T4BSS) substrates. PtVFX\/2014 also inherited a rare ~65\u2009kb pathogenicity island carrying virulence factors and detoxifying enzymes believed to contribute to the emergence of best-fitted strains in water reservoirs and in human macrophages, as well as a inter-species transferred (from <jats:italic>L. oakridgensis<\/jats:italic>) ~37.5\u2009kb genomic island (harboring a <jats:italic>lvh\/lvr<\/jats:italic> T4ASS cluster) that had never been found intact within <jats:italic>L. pneumophila<\/jats:italic> species. PtVFX\/2014 encodes another <jats:italic>lvh<\/jats:italic>\/<jats:italic>lvr<\/jats:italic> cluster near to CRISPR-associated genes, which may boost <jats:italic>L. pneumophila<\/jats:italic> transition from an environmental bacterium to a human pathogen. Overall, this unique genomic make-up may impact PtVFX\/2014 ability to adapt to diverse environments, and, ultimately, to be transmitted and cause human disease.<\/jats:p>","DOI":"10.1038\/srep26261","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T21:12:30Z","timestamp":1463778750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Legionella pneumophila strain associated with the first evidence of person-to-person transmission of Legionnaires\u2019 disease: a unique mosaic genetic backbone"],"prefix":"10.1038","volume":"6","author":[{"given":"V\u00edtor","family":"Borges","sequence":"first","affiliation":[]},{"given":"Alexandra","family":"Nunes","sequence":"additional","affiliation":[]},{"given":"Daniel A.","family":"Sampaio","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Machado","sequence":"additional","affiliation":[]},{"given":"Maria J.","family":"Sim\u00f5es","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o P.","family":"Gomes","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"BFsrep26261_CR1","first-page":"407","volume":"13","author":"A Dominguez","year":"2009","unstructured":"Dominguez, A. et al. Factors influencing the case-fatality rate of Legionnaires\u2019 disease. Int J Tuberc Lung Dis 13, 407\u2013412 (2009).","journal-title":"Int J Tuberc Lung Dis"},{"key":"BFsrep26261_CR2","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/S1473-3099(14)70713-3","volume":"14","author":"N Phin","year":"2014","unstructured":"Phin, N. et al. Epidemiology and clinical management of Legionnaires\u2019 disease. Lancet Infect Dis 14, 1011\u20131021 (2014).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep26261_CR3","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1086\/341087","volume":"186","author":"VL Yu","year":"2002","unstructured":"Yu, V. L. et al. Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey. J Infect Dis 186, 127\u2013128 (2002).","journal-title":"J Infect Dis"},{"key":"BFsrep26261_CR4","unstructured":"Centers for Disease Control and Prevention. Legionellosis\u2013United States, 2000\u20132009. MMWR Morb Mortal Wkly Rep 60, 1083\u20131086 (2011)."},{"key":"BFsrep26261_CR5","unstructured":"European Centre for Disease Prevention and Control. Legionnaires\u2019 disease in Europe, 2012. (ECDC, Stockholm, 2014)."},{"key":"BFsrep26261_CR6","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1128\/CMR.15.3.506-526.2002","volume":"15","author":"BS Fields","year":"2002","unstructured":"Fields, B. S., Benson, R. F. & Besser, R. E. Legionella and Legionnaires\u2019 disease: 25 years of investigation. Clin Microbiol Rev 15, 506\u2013526 (2002).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep26261_CR7","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1001\/archinte.1986.00360200183030","volume":"146","author":"RR Muder","year":"1986","unstructured":"Muder, R. R., Yu, V. L. & Woo, A. H. Mode of transmission of Legionella pneumophila. A critical review. Arch Intern Med 146, 1607\u20131612 (1986).","journal-title":"Arch Intern Med"},{"key":"BFsrep26261_CR8","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMc1505356","volume":"374","author":"AM Correia","year":"2016","unstructured":"Correia, A. M. et al. Probable Person-to-Person Transmission of Legionnaires\u2019 Disease. N Engl J Med 374, 497\u2013498 (2016).","journal-title":"N Engl J Med"},{"key":"BFsrep26261_CR9","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3201\/eid0908.030337","volume":"9","author":"A Garcia-Fulgueiras","year":"2003","unstructured":"Garcia-Fulgueiras, A. et al. Legionnaires\u2019 disease outbreak in Murcia, Spain. Emerg Infect Dis 9, 915\u2013921 (2003).","journal-title":"Emerg Infect Dis"},{"key":"BFsrep26261_CR10","doi-asserted-by":"crossref","unstructured":"Levesque, S. et al. Genomic characterization of a large outbreak of Legionella pneumophila serogroup 1 strains in Quebec City, 2012. Plos One 9, e103852 (2014).","DOI":"10.1371\/journal.pone.0103852"},{"key":"BFsrep26261_CR11","first-page":"504","volume":"15","author":"PR McAdam","year":"2014","unstructured":"McAdam, P. R. et al. Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires\u2019 disease outbreak. Genome Biol 15, 504 (2014).","journal-title":"Genome Biol"},{"key":"BFsrep26261_CR12","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1038\/ng.3114","volume":"46","author":"L Sanchez-Buso","year":"2014","unstructured":"Sanchez-Buso, L., Comas, I., Jorques, G. & Gonzalez-Candelas, F. Recombination drives genome evolution in outbreak-related Legionella pneumophila isolates. Nat Genet 46, 1205\u20131211 (2014).","journal-title":"Nat Genet"},{"key":"BFsrep26261_CR13","doi-asserted-by":"publisher","first-page":"20991","DOI":"10.2807\/1560-7917.ES2014.19.50.20991","volume":"19","author":"T Shivaji","year":"2014","unstructured":"Shivaji, T. et al. A large community outbreak of Legionnaires disease in Vila Franca de Xira, Portugal, October to November 2014. Euro Surveill 19, 20991 (2014).","journal-title":"Euro Surveill"},{"key":"BFsrep26261_CR14","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1056\/NEJM197712012972201","volume":"297","author":"DW Fraser","year":"1977","unstructured":"Fraser, D. W. et al. Legionnaires\u2019 disease: description of an epidemic of pneumonia. N Engl J Med 297, 1189\u20131197 (1977).","journal-title":"N Engl J Med"},{"key":"BFsrep26261_CR15","doi-asserted-by":"publisher","first-page":"4797","DOI":"10.1021\/acs.est.5b00142","volume":"49","author":"E van Heijnsbergen","year":"2015","unstructured":"van Heijnsbergen, E. et al. Confirmed and Potential Sources of Legionella Reviewed. Environ Sci Technol 49, 4797\u20134815 (2015).","journal-title":"Environ Sci Technol"},{"key":"BFsrep26261_CR16","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1128\/JCM.43.5.2047-2052.2005","volume":"43","author":"V Gaia","year":"2005","unstructured":"Gaia, V. et al. Consensus sequence-based scheme for epidemiological typing of clinical and environmental isolates of Legionella pneumophila . J Clin Microbiol 43, 2047\u20132052 (2005).","journal-title":"J Clin Microbiol"},{"key":"BFsrep26261_CR17","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1128\/JCM.00261-07","volume":"45","author":"S Ratzow","year":"2007","unstructured":"Ratzow, S., Gaia, V., Helbig, J. H., Fry, N. K. & Luck, P. C. Addition of neuA, the gene encoding N-acylneuraminate cytidylyl transferase, increases the discriminatory ability of the consensus sequence-based scheme for typing Legionella pneumophila serogroup 1 strains. J Clin Microbiol 45, 1965\u20131968 (2007).","journal-title":"J Clin Microbiol"},{"key":"BFsrep26261_CR18","doi-asserted-by":"publisher","first-page":"21186","DOI":"10.2807\/1560-7917.ES2015.20.28.21186","volume":"20","author":"J Moran-Gilad","year":"2015","unstructured":"Moran-Gilad, J. et al. Design and application of a core genome multilocus sequence typing scheme for investigation of Legionnaires\u2019 disease incidents. Euro Surveill 20, 21186 (2015).","journal-title":"Euro Surveill"},{"key":"BFsrep26261_CR19","doi-asserted-by":"publisher","first-page":"e002175","DOI":"10.1136\/bmjopen-2012-002175","volume":"3","author":"S Reuter","year":"2013","unstructured":"Reuter, S. et al. A pilot study of rapid whole-genome sequencing for the investigation of a Legionella outbreak. BMJ Open 3, e002175 (2013).","journal-title":"BMJ Open"},{"key":"BFsrep26261_CR20","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1186\/1471-2180-13-302","volume":"13","author":"AP Underwood","year":"2013","unstructured":"Underwood, A. P., Jones, G., Mentasti, M., Fry, N. K. & Harrison, T. G. Comparison of the Legionella pneumophila population structure as determined by sequence-based typing and whole genome sequencing. BMC Microbiol 13, 302 (2013).","journal-title":"BMC Microbiol"},{"key":"BFsrep26261_CR21","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1017\/S0950268814000375","volume":"142","author":"RM Graham","year":"2014","unstructured":"Graham, R. M., Doyle, C. J. & Jennison, A. V. Real-time investigation of a Legionella pneumophila outbreak using whole genome sequencing. Epidemiol Infect 142, 2347\u20132351 (2014).","journal-title":"Epidemiol Infect"},{"key":"BFsrep26261_CR22","unstructured":"Pinto, C. S. A large outbreak of Legionnaires\u2019 Disease in Vila Franca de Xira, Portugal. Paper presented at Third Annual Scientific Conference of the the European Working Group for Legionella Infections (ESCMID) Study Group for Legionella infections (ESGLI) (ESGLI 2015), ESCMID. London. 2015, 16\u201317 September."},{"key":"BFsrep26261_CR23","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1186\/1471-2164-12-536","volume":"12","author":"L Gomez-Valero","year":"2011","unstructured":"Gomez-Valero, L. et al. Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes. BMC Genomics 12, 536 (2011).","journal-title":"BMC Genomics"},{"key":"BFsrep26261_CR24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/1471-2164-11-181","volume":"11","author":"G D\u2019Auria","year":"2010","unstructured":"D\u2019Auria, G., Jimenez-Hernandez, N., Peris-Bondia, F., Moya, A. & Latorre, A. Legionella pneumophila pangenome reveals strain-specific virulence factors. BMC Genomics 11, 181 (2010).","journal-title":"BMC Genomics"},{"key":"BFsrep26261_CR25","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1093\/molbev\/msq278","volume":"28","author":"M Coscolla","year":"2011","unstructured":"Coscolla, M., Comas, I. & Gonzalez-Candelas, F. Quantifying nonvertical inheritance in the evolution of Legionella pneumophila . Mol Biol Evol 28, 985\u20131001 (2011).","journal-title":"Mol Biol Evol"},{"key":"BFsrep26261_CR26","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1038\/ng1447","volume":"36","author":"C Cazalet","year":"2004","unstructured":"Cazalet, C. et al. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat Genet 36, 1165\u20131173 (2004).","journal-title":"Nat Genet"},{"key":"BFsrep26261_CR27","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1128\/JB.00778-10","volume":"192","author":"GN Schroeder","year":"2010","unstructured":"Schroeder, G. N. et al. Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot\/Icm secretion system effector proteins. J Bacteriol 192, 6001\u20136016 (2010).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR28","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.mib.2008.12.004","volume":"12","author":"AW Ensminger","year":"2009","unstructured":"Ensminger, A. W. & Isberg, R. R. Legionella pneumophila Dot\/Icm translocated substrates: a sum of parts. Curr Opin Microbiol 12, 67\u201373 (2009).","journal-title":"Curr Opin Microbiol"},{"key":"BFsrep26261_CR29","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1073\/pnas.0304916101","volume":"101","author":"ZQ Luo","year":"2004","unstructured":"Luo, Z. Q. & Isberg, R. R. Multiple substrates of the Legionella pneumophila Dot\/Icm system identified by interbacterial protein transfer. Proc Natl Acad Sci USA 101, 841\u2013846 (2004).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep26261_CR30","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.ijmm.2007.07.012","volume":"298","author":"G Glockner","year":"2008","unstructured":"Glockner, G. et al. Identification and characterization of a new conjugation\/type IVA secretion system (trb\/tra) of Legionella pneumophila Corby localized on two mobile genomic islands. Int J Med Microbiol 298, 411\u2013428 (2008).","journal-title":"Int J Med Microbiol"},{"key":"BFsrep26261_CR31","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ijmm.2007.03.009","volume":"297","author":"M Steinert","year":"2007","unstructured":"Steinert, M., Heuner, K., Buchrieser, C., Albert-Weissenberger, C. & Glockner, G. Legionella pathogenicity: genome structure, regulatory networks and the host cell response. Int J Med Microbiol 297, 577\u2013587 (2007).","journal-title":"Int J Med Microbiol"},{"key":"BFsrep26261_CR32","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1016\/j.febslet.2007.05.026","volume":"581","author":"M Jules","year":"2007","unstructured":"Jules, M. & Buchrieser, C. Legionella pneumophila adaptation to intracellular life and the host response: clues from genomics and transcriptomics. FEBS Lett 581, 2829\u20132838 (2007).","journal-title":"FEBS Lett"},{"key":"BFsrep26261_CR33","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/j.1758-2229.2011.00247.x","volume":"3","author":"H Hilbi","year":"2011","unstructured":"Hilbi, H., Hoffmann, C. & Harrison, C. F. Legionella spp. outdoors: colonization, communication and persistence. Environ Microbiol Rep 3, 286\u2013296 (2011).","journal-title":"Environ Microbiol Rep"},{"key":"BFsrep26261_CR34","doi-asserted-by":"publisher","first-page":"6647","DOI":"10.1128\/AEM.01957-13","volume":"79","author":"B Cao","year":"2013","unstructured":"Cao, B., Yao, F., Liu, X., Feng, L. & Wang, L. Development of a DNA microarray method for detection and identification of all 15 distinct O-antigen forms of Legionella pneumophila . Appl Environ Microbiol 79, 6647\u20136654 (2013).","journal-title":"Appl Environ Microbiol"},{"key":"BFsrep26261_CR35","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1101\/gr.7229808","volume":"18","author":"C Cazalet","year":"2008","unstructured":"Cazalet, C. et al. Multigenome analysis identifies a worldwide distributed epidemic Legionella pneumophila clone that emerged within a highly diverse species. Genome Res 18, 431\u2013441 (2008).","journal-title":"Genome Res"},{"key":"BFsrep26261_CR36","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1126\/science.1099776","volume":"305","author":"M Chien","year":"2004","unstructured":"Chien, M. et al. The genomic sequence of the accidental pathogen Legionella pneumophila . Science 305, 1966\u20131968 (2004).","journal-title":"Science"},{"key":"BFsrep26261_CR37","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1128\/IAI.68.3.1069-1079.2000","volume":"68","author":"VK Viswanathan","year":"2000","unstructured":"Viswanathan, V. K., Edelstein, P. H., Pope, C. D. & Cianciotto, N. P. The Legionella pneumophila iraAB locus is required for iron assimilation, intracellular infection, and virulence. Infect Immun 68, 1069\u20131079 (2000).","journal-title":"Infect Immun"},{"key":"BFsrep26261_CR38","doi-asserted-by":"publisher","first-page":"8231","DOI":"10.1128\/JB.00937-06","volume":"188","author":"CD Vincent","year":"2006","unstructured":"Vincent, C. D. et al. Identification of non-dot\/icm suppressors of the Legionella pneumophila DeltadotL lethality phenotype. J Bacteriol 188, 8231\u20138243 (2006).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR39","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/1471-2180-13-198","volume":"13","author":"M Petzold","year":"2013","unstructured":"Petzold, M. et al. A structural comparison of lipopolysaccharide biosynthesis loci of Legionella pneumophila serogroup 1 strains. BMC Microbiol 13, 198 (2013).","journal-title":"BMC Microbiol"},{"key":"BFsrep26261_CR40","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.1128\/iai.63.12.4576-4583.1995","volume":"63","author":"E Wintermeyer","year":"1995","unstructured":"Wintermeyer, E. et al. Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells. Infect Immun 63, 4576\u20134583 (1995).","journal-title":"Infect Immun"},{"key":"BFsrep26261_CR41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3389\/fmicb.2011.00074","volume":"2","author":"O Shevchuk","year":"2011","unstructured":"Shevchuk, O., Jager, J. & Steinert, M. Virulence properties of the Legionella pneumophila cell envelope. Front Microbiol 2, 74 (2011).","journal-title":"Front Microbiol"},{"key":"BFsrep26261_CR42","doi-asserted-by":"publisher","first-page":"8126","DOI":"10.1128\/JB.01035-08","volume":"190","author":"X Charpentier","year":"2008","unstructured":"Charpentier, X., Faucher, S. P., Kalachikov, S. & Shuman, H. A. Loss of RNase R induces competence development in Legionella pneumophila . J Bacteriol 190, 8126\u20138136 (2008).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR43","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nrmicro1526","volume":"4","author":"GR Cornelis","year":"2006","unstructured":"Cornelis, G. R. The type III secretion injectisome. Nat Rev Microbiol 4, 811\u2013825 (2006).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep26261_CR44","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrmicro1967","volume":"7","author":"RR Isberg","year":"2009","unstructured":"Isberg, R. R., O\u2019Connor, T. J. & Heidtman, M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat Rev Microbiol 7, 13\u201324 (2009).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep26261_CR45","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.tim.2007.06.006","volume":"15","author":"S Ninio","year":"2007","unstructured":"Ninio, S. & Roy, C. R. Effector proteins translocated by Legionella pneumophila: strength in numbers. Trends Microbiol 15, 372\u2013380 (2007).","journal-title":"Trends Microbiol"},{"key":"BFsrep26261_CR46","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1128\/JB.01175-13","volume":"196","author":"O Nevo","year":"2014","unstructured":"Nevo, O., Zusman, T., Rasis, M., Lifshitz, Z. & Segal, G. Identification of Legionella pneumophila effectors regulated by the LetAS-RsmYZ-CsrA regulatory cascade, many of which modulate vesicular trafficking. J Bacteriol 196, 681\u2013692 (2014).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR47","doi-asserted-by":"publisher","first-page":"e17638","DOI":"10.1371\/journal.pone.0017638","volume":"6","author":"W Zhu","year":"2011","unstructured":"Zhu, W. et al. Comprehensive identification of protein substrates of the Dot\/Icm type IV transporter of Legionella pneumophila . PLoS One 6, e17638 (2011).","journal-title":"PLoS One"},{"key":"BFsrep26261_CR48","doi-asserted-by":"publisher","first-page":"841","DOI":"10.4049\/jimmunol.1200794","volume":"189","author":"SS Weber","year":"2012","unstructured":"Weber, S. S. et al. Identification of protective B cell antigens of Legionella pneumophila . J Immunol 189, 841\u2013849 (2012).","journal-title":"J Immunol"},{"key":"BFsrep26261_CR49","first-page":"505","volume":"15","author":"L Gomez-Valero","year":"2014","unstructured":"Gomez-Valero, L. et al. Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires\u2019 disease. Genome Biol 15, 505 (2014).","journal-title":"Genome Biol"},{"key":"BFsrep26261_CR50","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.ijmm.2013.07.003","volume":"303","author":"E Brzuszkiewicz","year":"2013","unstructured":"Brzuszkiewicz, E. et al. Legionella oakridgensis ATCC 33761 genome sequence and phenotypic characterization reveals its replication capacity in amoebae. Int J Med Microbiol 303, 514\u2013528 (2013).","journal-title":"Int J Med Microbiol"},{"key":"BFsrep26261_CR51","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1046\/j.1365-2958.1999.01642.x","volume":"34","author":"G Segal","year":"1999","unstructured":"Segal, G., Russo, J. J. & Shuman, H. A. Relationships between a new type IV secretion system and the icm\/dot virulence system of Legionella pneumophila . Mol Microbiol 34, 799\u2013809 (1999).","journal-title":"Mol Microbiol"},{"key":"BFsrep26261_CR52","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1128\/IAI.00956-06","volume":"75","author":"P Bandyopadhyay","year":"2007","unstructured":"Bandyopadhyay, P., Liu, S., Gabbai, C. B., Venitelli, Z. & Steinman, H. M. Environmental mimics and the Lvh type IVA secretion system contribute to virulence-related phenotypes of Legionella pneumophila . Infect Immun 75, 723\u2013735 (2007).","journal-title":"Infect Immun"},{"key":"BFsrep26261_CR53","doi-asserted-by":"publisher","first-page":"2238","DOI":"10.1128\/jb.171.4.2238-2240.1989","volume":"171","author":"A Marra","year":"1989","unstructured":"Marra, A. & Shuman, H. A. Isolation of a Legionella pneumophila restriction mutant with increased ability to act as a recipient in heterospecific matings. J Bacteriol 171, 2238\u20132240 (1989).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR54","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1126\/science.1179555","volume":"327","author":"P Horvath","year":"2010","unstructured":"Horvath, P. & Barrangou, R. CRISPR\/Cas, the immune system of bacteria and archaea. Science 327, 167\u2013170 (2010).","journal-title":"Science"},{"key":"BFsrep26261_CR55","first-page":"98","volume":"2","author":"SP Faucher","year":"2011","unstructured":"Faucher, S. P. & Shuman, H. A. Small Regulatory RNA and Legionella pneumophila . Front Microbiol 2, 98 (2011).","journal-title":"Front Microbiol"},{"key":"BFsrep26261_CR56","doi-asserted-by":"publisher","first-page":"e00074","DOI":"10.1128\/mBio.00074-13","volume":"4","author":"FF Gunderson","year":"2013","unstructured":"Gunderson, F. F. & Cianciotto, N. P. The CRISPR-associated gene cas2 of Legionella pneumophila is required for intracellular infection of amoebae. MBio 4, e00074\u201300013 (2013).","journal-title":"MBio"},{"key":"BFsrep26261_CR57","doi-asserted-by":"publisher","first-page":"e01091","DOI":"10.1128\/mBio.01091-14","volume":"5","author":"KJ Flynn","year":"2014","unstructured":"Flynn, K. J. & Swanson, M. S. Integrative conjugative element ICE-betaox confers oxidative stress resistance to Legionella pneumophila in vitro and in macrophages. MBio 5, e01091\u201301014 (2014).","journal-title":"MBio"},{"key":"BFsrep26261_CR58","doi-asserted-by":"publisher","first-page":"4630","DOI":"10.1128\/JB.185.15.4630-4637.2003","volume":"185","author":"AK Brassinga","year":"2003","unstructured":"Brassinga, A. K. et al. A 65-kilobase pathogenicity island is unique to Philadelphia-1 strains of Legionella pneumophila . J Bacteriol 185, 4630\u20134637 (2003).","journal-title":"J Bacteriol"},{"key":"BFsrep26261_CR59","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1128\/AAC.00475-08","volume":"52","author":"F Long","year":"2008","unstructured":"Long, F., Rouquette-Loughlin, C., Shafer, W. M. & Yu, E. W. Functional cloning and characterization of the multidrug efflux pumps NorM from Neisseria gonorrhoeae and YdhE from Escherichia coli . Antimicrob Agents Chemother 52, 3052\u20133060 (2008).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep26261_CR60","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1006\/mpat.1993.1095","volume":"15","author":"H Miyamoto","year":"1993","unstructured":"Miyamoto, H. et al. Protein profiles of Legionella pneumophila Philadelphia-1 grown in macrophages and characterization of a gene encoding a novel 24 kDa Legionella protein. Microb Pathog 15, 469\u2013484 (1993).","journal-title":"Microb Pathog"},{"key":"BFsrep26261_CR61","doi-asserted-by":"publisher","first-page":"e00595","DOI":"10.1128\/mBio.00595-15","volume":"6","author":"ZD Abbott","year":"2015","unstructured":"Abbott, Z. D., Yakhnin, H., Babitzke, P. & Swanson, M. S. csrR, a paralog and direct target of CsrA, promotes Legionella pneumophila resilience in water. MBio 6, e00595 (2015).","journal-title":"MBio"},{"key":"BFsrep26261_CR62","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.ijmm.2003.12.003","volume":"294","author":"V Forsbach-Birk","year":"2004","unstructured":"Forsbach-Birk, V., McNealy, T., Shi, C., Lynch, D. & Marre, R. Reduced expression of the global regulator protein CsrA in Legionella pneumophila affects virulence-associated regulators and growth in Acanthamoeba castellanii . Int J Med Microbiol 294, 15\u201325 (2004).","journal-title":"Int J Med Microbiol"},{"key":"BFsrep26261_CR63","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1046\/j.1365-2958.2003.03706.x","volume":"50","author":"AB Molofsky","year":"2003","unstructured":"Molofsky, A. B. & Swanson, M. S. Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication. Mol Microbiol 50, 445\u2013461 (2003).","journal-title":"Mol Microbiol"},{"key":"BFsrep26261_CR64","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fmicb.2011.00208","volume":"2","author":"L Gomez-Valero","year":"2011","unstructured":"Gomez-Valero, L., Rusniok, C., Cazalet, C. & Buchrieser, C. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol 2, 208 (2011).","journal-title":"Front Microbiol"},{"key":"BFsrep26261_CR65","doi-asserted-by":"publisher","first-page":"E707","DOI":"10.1073\/pnas.1215278110","volume":"110","author":"Z Lifshitz","year":"2013","unstructured":"Lifshitz, Z. et al. Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal. Proc Natl Acad Sci USA 110, E707\u2013715 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep26261_CR66","doi-asserted-by":"publisher","first-page":"e1000117","DOI":"10.1371\/journal.ppat.1000117","volume":"4","author":"KS de Felipe","year":"2008","unstructured":"de Felipe, K. S. et al. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog 4, e1000117 (2008).","journal-title":"PLoS Pathog"},{"key":"BFsrep26261_CR67","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1111\/j.1462-5822.2011.01710.x","volume":"13","author":"J Ge","year":"2011","unstructured":"Ge, J. & Shao, F. Manipulation of host vesicular trafficking and innate immune defence by Legionella Dot\/Icm effectors. Cell Microbiol 13, 1870\u20131880 (2011).","journal-title":"Cell Microbiol"},{"key":"BFsrep26261_CR68","doi-asserted-by":"publisher","first-page":"343","DOI":"10.2217\/fmb.13.162","volume":"9","author":"DT Isaac","year":"2014","unstructured":"Isaac, D. T. & Isberg, R. Master manipulators: an update on Legionella pneumophila Icm\/Dot translocated substrates and their host targets. Future Microbiol 9, 343\u2013359 (2014).","journal-title":"Future Microbiol"},{"key":"BFsrep26261_CR69","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1111\/j.1462-5822.2010.01467.x","volume":"12","author":"M Lomma","year":"2010","unstructured":"Lomma, M. et al. The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell Microbiol 12, 1272\u20131291 (2010).","journal-title":"Cell Microbiol"},{"key":"BFsrep26261_CR70","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1126\/science.1158160","volume":"320","author":"X Pan","year":"2008","unstructured":"Pan, X., Luhrmann, A., Satoh, A., Laskowski-Arce, M. A. & Roy, C. R. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 320, 1651\u20131654 (2008).","journal-title":"Science"},{"key":"BFsrep26261_CR71","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1002\/eji.201242835","volume":"43","author":"AA Khweek","year":"2013","unstructured":"Khweek, A. A. et al. A bacterial protein promotes the recognition of the Legionella pneumophila vacuole by autophagy. Eur J Immunol 43, 1333\u20131344 (2013).","journal-title":"Eur J Immunol"},{"key":"BFsrep26261_CR72","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/1471-2105-10-152","volume":"10","author":"AP Francisco","year":"2009","unstructured":"Francisco, A. P., Bugalho, M., Ramirez, M. & Carrico, J. A. Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics 10, 152 (2009).","journal-title":"BMC Bioinformatics"},{"key":"BFsrep26261_CR73","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/1471-2105-13-87","volume":"13","author":"AP Francisco","year":"2012","unstructured":"Francisco, A. P. et al. PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13, 87 (2012).","journal-title":"BMC Bioinformatics"},{"key":"BFsrep26261_CR74","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1186\/s13059-014-0524-x","volume":"15","author":"TJ Treangen","year":"2014","unstructured":"Treangen, T. J., Ondov, B. D., Koren, S. & Phillippy, A. M. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 15, 524 (2014).","journal-title":"Genome Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep26261.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26261","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26261.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T04:20:31Z","timestamp":1672892431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep26261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,19]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,5,31]]}},"alternative-id":["BFsrep26261"],"URL":"https:\/\/doi.org\/10.1038\/srep26261","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,19]]},"assertion":[{"value":"25 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26261"}}