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Abstract

Introduction

Whole genome sequencing (WGS) is increasingly used in Legionnaires’ disease (LD) outbreak investigations, owing to its higher resolution than sequence-based typing, the gold standard typing method for in the analysis of endemic strains. Recently, a gene-by-gene typing approach based on 1,521 core genes called core genome multilocus sequence typing (cgMLST) was described that enables a robust and standardised typing of . : We applied this cgMLST scheme to isolates obtained during the largest outbreak of LD reported so far in Germany. In this outbreak, the epidemic clone ST345 had been isolated from patients and four different environmental sources. In total 42 clinical and environmental isolates were retrospectively typed. : Epidemiologically unrelated ST345 isolates were clearly distinguishable from the epidemic clone. Remarkably, epidemic isolates split up into two distinct clusters, ST345-A and ST345-B, each respectively containing a mix of clinical and epidemiologically-related environmental samples. : The outbreak was therefore likely caused by both variants of the single sequence type, which pre-existed in the environmental reservoirs. The two clusters differed by 40 alleles located in two neighbouring genomic regions of ca 42 and 26 kb. Additional analysis supported horizontal gene transfer of the two regions as responsible for the difference between the variants. Both regions comprise virulence genes and have previously been reported to be involved in recombination events. This corroborates the notion that genomic outbreak investigations should always take epidemiological information into consideration when making inferences. Overall, cgMLST proved helpful in disentangling the complex genomic epidemiology of the outbreak.

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2017-11-09
2024-12-26
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References

  1. Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG, et al. Legionnaires’ disease: description of an epidemic of pneumonia. N Engl J Med. 1977;297(22):1189-97.  https://doi.org/10.1056/NEJM197712012972201  PMID: 335244 
  2. McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR. Legionnaires’ disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N Engl J Med. 1977;297(22):1197-203.  https://doi.org/10.1056/NEJM197712012972202  PMID: 335245 
  3. Correia AM, Ferreira JS, Borges V, Nunes A, Gomes B, Capucho R, et al. Probable person-to-person transmission of Legionnaires’ Disease. N Engl J Med. 2016;374(5):497-8.  https://doi.org/10.1056/NEJMc1505356  PMID: 26840151 
  4. Torres A, Blasi F, Peetermans WE, Viegi G, Welte T. The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: a literature review. Eur J Clin Microbiol Infect Dis. 2014;33(7):1065-79.  https://doi.org/10.1007/s10096-014-2067-1  PMID: 24532008 
  5. Robert-Koch-Institut. Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2015. Berlin: Robert-Koch-Institut; 2016. 138-44 p.
  6. Bajrai LH, Azhar EI, Yasir M, Jardot P, Barrassi L, Raoult D, et al. Legionella saoudiensis sp. nov., isolated from a sewage water sample. Int J Syst Evol Microbiol. 2016;66(11):4367-71.  https://doi.org/10.1099/ijsem.0.001357  PMID: 27489234 
  7. European Centre for Disease Prevention and Control (ECDC). Legionnaires’ disease in Europe, 2013. Stockholm: ECDC; 2015.
  8. Walser SM, Gerstner DG, Brenner B, Höller C, Liebl B, Herr CE. Assessing the environmental health relevance of cooling towers--a systematic review of legionellosis outbreaks. Int J Hyg Environ Health. 2014;217(2-3):145-54.  https://doi.org/10.1016/j.ijheh.2013.08.002  PMID: 24100053 
  9. Helbig JH, Bernander S, Castellani Pastoris M, Etienne J, Gaia V, Lauwers S, et al. Pan-European study on culture-proven Legionnaires’ disease: distribution of Legionella pneumophila serogroups and monoclonal subgroups. Eur J Clin Microbiol Infect Dis. 2002;21(10):710-6.  https://doi.org/10.1007/s10096-002-0820-3  PMID: 12415469 
  10. ESGLI. The ESGLI SBT database for the typing of Legionella pneumophila 2015. Available from: http://www.hpa-bioinformatics.org.uk/legionella/legionella_sbt/php/sbt_homepage.php
  11. Sabat AJ, Budimir A, Nashev D, Sá-Leão R, van Dijl J, Laurent F, et al. Overview of molecular typing methods for outbreak detection and epidemiological surveillance. Euro Surveill. 2013;18(4):20380.  https://doi.org/10.2807/ese.18.04.20380-en  PMID: 23369389 
  12. van Belkum A, Tassios PT, Dijkshoorn L, Haeggman S, Cookson B, Fry NK, et al. , European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Epidemiological Markers (ESGEM). Guidelines for the validation and application of typing methods for use in bacterial epidemiology. Clin Microbiol Infect. 2007;13(Suppl 3):1-46.  https://doi.org/10.1111/j.1469-0691.2007.01786.x  PMID: 17716294 
  13. David S, Rusniok C, Mentasti M, Gomez-Valero L, Harris SR, Lechat P, et al. Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently. Genome Res. 2016;26(11):1555-64.  https://doi.org/10.1101/gr.209536.116  PMID: 27662900 
  14. Ginevra C, Jacotin N, Diancourt L, Guigon G, Arquilliere R, Meugnier H, et al. Legionella pneumophila sequence type 1/Paris pulsotype subtyping by spoligotyping. J Clin Microbiol. 2012;50(3):696-701.  https://doi.org/10.1128/JCM.06180-11  PMID: 22205819 
  15. Graham RM, Doyle CJ, Jennison AV. Real-time investigation of a Legionella pneumophila outbreak using whole genome sequencing. Epidemiol Infect. 2014;142(11):2347-51.  https://doi.org/10.1017/S0950268814000375  PMID: 24576553 
  16. Lévesque S, Plante PL, Mendis N, Cantin P, Marchand G, Charest H, et al. Genomic characterization of a large outbreak of Legionella pneumophila serogroup 1 strains in Quebec City, 2012. PLoS One. 2014;9(8):e103852.  https://doi.org/10.1371/journal.pone.0103852  PMID: 25105285 
  17. McAdam PR, Vander Broek CW, Lindsay DS, Ward MJ, Hanson MF, Gillies M, et al. Gene flow in environmental Legionella pneumophila leads to genetic and pathogenic heterogeneity within a Legionnaires’ disease outbreak. Genome Biol. 2014;15(11):504. PMID: 25370747 
  18. Moran-Gilad J, Prior K, Yakunin E, Harrison TG, Underwood A, Lazarovitch T, et al. Design and application of a core genome multilocus sequence typing scheme for investigation of Legionnaires’ disease incidents. Euro Surveill. 2015;20(28):21186.  https://doi.org/10.2807/1560-7917.ES2015.20.28.21186  PMID: 26212142 
  19. Raphael BH, Baker DJ, Nazarian E, Lapierre P, Bopp D, Kozak-Muiznieks NA, et al. Genomic resolution of outbreak-associated Legionella pneumophila serogroup 1 isolates from New York State. Appl Environ Microbiol. 2016;82(12):3582-90.  https://doi.org/10.1128/AEM.00362-16  PMID: 27060122 
  20. Reuter S, Harrison TG, Köser CU, Ellington MJ, Smith GP, Parkhill J, et al. A pilot study of rapid whole-genome sequencing for the investigation of a Legionella outbreak. BMJ Open. 2013;3(1):e002175.  https://doi.org/10.1136/bmjopen-2012-002175  PMID: 23306006 
  21. Maiden MC, Jansen van Rensburg MJ, Bray JE, Earle SG, Ford SA, Jolley KA, et al. MLST revisited: the gene-by-gene approach to bacterial genomics. Nat Rev Microbiol. 2013;11(10):728-36.  https://doi.org/10.1038/nrmicro3093  PMID: 23979428 
  22. Burckhardt F, Brion A, Lahm J, Koch HU, Prior K, Petzold M, et al. Confirming Legionnaires’ disease outbreak by genome-based method, Germany, 2012. Emerg Infect Dis. 2016;22(7):1303-4.  https://doi.org/10.3201/eid2207.151738  PMID: 27315051 
  23. Maisa A, Brockmann A, Renken F, Lück C, Pleischl S, Exner M, et al. Epidemiological investigation and case-control study: a Legionnaires’ disease outbreak associated with cooling towers in Warstein, Germany, August-September 2013. Euro Surveill. 2015;20(46):30064.  https://doi.org/10.2807/1560-7917.ES.2015.20.46.30064  PMID: 26607018 
  24. Essig A, von Baum H, Gonser T, Haerter G, Lück C. Microbiological diagnosis and molecular typing of Legionella strains during an outbreak of legionellosis in Southern Germany. Int J Med Microbiol. 2016;306(2):109-14.  https://doi.org/10.1016/j.ijmm.2016.01.001  PMID: 26868659 
  25. Petzold M, Ehricht R, Slickers P, Pleischl S, Brockmann A, Exner M, et al. Rapid genotyping of Legionella pneumophila serogroup 1 strains by a novel DNA microarray-based assay during the outbreak investigation in Warstein, Germany 2013. Int J Hyg Environ Health. 2017;220(4):673-8.  https://doi.org/10.1016/j.ijheh.2016.02.004  PMID: 28501485 
  26. Mérault N, Rusniok C, Jarraud S, Gomez-Valero L, Cazalet C, Marin M, et al. , DELPH-I Study Group. Specific real-time PCR for simultaneous detection and identification of Legionella pneumophila serogroup 1 in water and clinical samples. Appl Environ Microbiol. 2011;77(5):1708-17.  https://doi.org/10.1128/AEM.02261-10  PMID: 21193672 
  27. Mentasti M, Fry NK, Afshar B, Palepou-Foxley C, Naik FC, Harrison TG. Application of Legionella pneumophila-specific quantitative real-time PCR combined with direct amplification and sequence-based typing in the diagnosis and epidemiological investigation of Legionnaires’ disease. Eur J Clin Microbiol Infect Dis. 2012;31(8):2017-28.  https://doi.org/10.1007/s10096-011-1535-0  PMID: 22278293 
  28. Jünemann S, Sedlazeck FJ, Prior K, Albersmeier A, John U, Kalinowski J, et al. Updating benchtop sequencing performance comparison. Nat Biotechnol. 2013;31(4):294-6.  https://doi.org/10.1038/nbt.2522  PMID: 23563421 
  29. Zerbino DR, Birney E. Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res. 2008;18(5):821-9.  https://doi.org/10.1101/gr.074492.107  PMID: 18349386 
  30. Darling AE, Mau B, Perna NT. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PLoS One. 2010;5(6):e11147.  https://doi.org/10.1371/journal.pone.0011147  PMID: 20593022 
  31. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA, Bentley SD, et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res. 2015;43(3):e15.  https://doi.org/10.1093/nar/gku1196  PMID: 25414349 
  32. Ensminger AW, Isberg RR. Legionella pneumophila Dot/Icm translocated substrates: a sum of parts. Curr Opin Microbiol. 2009;12(1):67-73.  https://doi.org/10.1016/j.mib.2008.12.004  PMID: 19157961 
  33. Liu M, Haenssler E, Uehara T, Losick VP, Park JT, Isberg RR. The Legionella pneumophila EnhC protein interferes with immunostimulatory muramyl peptide production to evade innate immunity. Cell Host Microbe. 2012;12(2):166-76.  https://doi.org/10.1016/j.chom.2012.06.004  PMID: 22901537 
  34. Mercante JW, Winchell JM. Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev. 2015;28(1):95-133.  https://doi.org/10.1128/CMR.00029-14  PMID: 25567224 
  35. Phin N, Parry-Ford F, Harrison T, Stagg HR, Zhang N, Kumar K, et al. Epidemiology and clinical management of Legionnaires’ disease. Lancet Infect Dis. 2014;14(10):1011-21.  https://doi.org/10.1016/S1473-3099(14)70713-3  PMID: 24970283 
  36. Sánchez-Busó L, Guiral S, Crespi S, Moya V, Camaró ML, Olmos MP, et al. Genomic Investigation of a Legionellosis Outbreak in a Persistently Colonized Hotel. Front Microbiol. 2016;6:1556.  https://doi.org/10.3389/fmicb.2015.01556  PMID: 26834713 
  37. Sánchez-Busó L, Comas I, Jorques G, González-Candelas F. Recombination drives genome evolution in outbreak-related Legionella pneumophila isolates. Nat Genet. 2014;46(11):1205-11.  https://doi.org/10.1038/ng.3114  PMID: 25282102 
  38. Marttinen P, Hanage WP, Croucher NJ, Connor TR, Harris SR, Bentley SD, et al. Detection of recombination events in bacterial genomes from large population samples. Nucleic Acids Res. 2012;40(1):e6.  https://doi.org/10.1093/nar/gkr928  PMID: 22064866 
  39. Mercante JW, Morrison SS, Desai HP, Raphael BH, Winchell JM. Genomic Analysis Reveals Novel Diversity among the 1976 Philadelphia Legionnaires’ Disease Outbreak Isolates and Additional ST36 Strains. PLoS One. 2016;11(9):e0164074.  https://doi.org/10.1371/journal.pone.0164074  PMID: 27684472 
  40. David S, Mentasti M, Tewolde R, Aslett M, Harris SR, Afshar B, et al. Evaluation of an Optimal Epidemiological Typing Scheme for Legionella pneumophila with Whole-Genome Sequence Data Using Validation Guidelines. J Clin Microbiol. 2016;54(8):2135-48.  https://doi.org/10.1128/JCM.00432-16  PMID: 27280420 
  41. Gordon M, Yakunin E, Valinsky L, Chalifa-Caspi V, Moran-Gilad J, ESCMID Study Group for Legionella Infections. A bioinformatics tool for ensuring the backwards compatibility of Legionella pneumophila typing in the genomic era. Clin Microbiol Infect. 2017;23(5):306-10.  https://doi.org/10.1016/j.cmi.2017.01.002  PMID: 28082190 
Epidemiological information is key when interpreting whole genome sequence data – lessons learned from a large Legionella pneumophila outbreak in Warstein, Germany, 2013
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Markus+Petzold&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Petzold Markus</a>, <a href="/search?value1=Karola+Prior&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Prior Karola</a>, <a href="/search?value1=Jacob+Moran-Gilad&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Moran-Gilad Jacob</a>, <a href="/search?value1=Dag+Harmsen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Harmsen Dag</a>, <a href="/search?value1=Christian+L%C3%BCck&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lück Christian</a></span>. Epidemiological information is key when interpreting whole genome sequence data – lessons learned from a large Legionella pneumophila outbreak in Warstein, Germany, 2013. <a href="/content/ecdc">Euro Surveill.</a> 2017;22(45):pii=17-00137. <a href="https://doi.org/10.2807/1560-7917.ES.2017.22.45.17-00137" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2017.22.45.17-00137</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 21 Feb 2017;&nbsp;&nbsp; <span class="generated">Accepted</span>: 18 Jul 2017 </span> </p>
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