Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently.
Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission.
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA Cambridge, United Kingdom.|Public Health England, NW9 5HT London, United Kingdom.
Sophia
S
David
Institut Pasteur, Biologie des Bactéries Intracellulaires, 75015, Paris, France.|CNRS UMR 3525, 75724, Paris, France.
Christophe
C
Rusniok
Public Health England, NW9 5HT London, United Kingdom.
Massimo
M
Mentasti
Institut Pasteur, Biologie des Bactéries Intracellulaires, 75015, Paris, France.|CNRS UMR 3525, 75724, Paris, France.
Laura
L
Gomez-Valero
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA Cambridge, United Kingdom.
Simon R
SR
Harris
Hub de Bio-informatique et Biostatistiques, Centre de Bio-informatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, 75724, Paris, France.
Pierre
P
Lechat
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA Cambridge, United Kingdom.
John
J
Lees
National Reference Centre for Legionella, Hospice Civil de Lyon, International Center for Infection Research, Legionella pathogenesis Team, 69364, Lyon, France.
Christophe
C
Ginevra
CNRS UMR 3525, 75724, Paris, France.|Institut Pasteur, Evolution et Ecologie de la Resistance aux Antibiotiques, 75724, Paris, France.
Philippe
P
Glaser
Institut Pasteur, Plate-Forme Génomique, 75724, Paris, France.
Laurence
L
Ma
Institut Pasteur, Plate-Forme Génomique, 75724, Paris, France.
Christiane
C
Bouchier
Public Health England, NW9 5HT London, United Kingdom.
Anthony
A
Underwood
National Reference Centre for Legionella, Hospice Civil de Lyon, International Center for Infection Research, Legionella pathogenesis Team, 69364, Lyon, France.
Sophie
S
Jarraud
Public Health England, NW9 5HT London, United Kingdom.
Timothy G
TG
Harrison
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA Cambridge, United Kingdom.
Julian
J
Parkhill
Institut Pasteur, Biologie des Bactéries Intracellulaires, 75015, Paris, France.|CNRS UMR 3525, 75724, Paris, France.
Carmen
C
Buchrieser
D019143:Evolution, Molecular; D006801:Humans; D016952:Legionella pneumophila / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D007877:Legionnaires' Disease / Q000382:microbiology*; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D014774:Virulence / Q000235:genetics
PLoS One. 2015 Jul 21;10(7):e0133727
26196384
Bioinformatics. 2006 Nov 1;22(21):2688-90
16928733
Clin Infect Dis. 2009 Jul 15;49(2):192-4
19508166
FEMS Microbiol Lett. 2004 Dec 15;241(2):249-56
15598540
Bioinformatics. 2015 Nov 15;31(22):3691-3
26198102
New Microbes New Infect. 2014 Nov 12;3:29-33
25755889
Clin Microbiol Rev. 2010 Apr;23(2):274-98
20375353
Genome Biol. 2012 Jun 25;13(6):R56
22731987
Nat Genet. 2004 Nov;36(11):1165-73
15467720
Clin Microbiol Rev. 2002 Jul;15(3):506-26
12097254
Nat Genet. 2014 Nov;46(11):1205-11
25282102
Infect Immun. 2002 Apr;70(4):1842-52
11895946
Science. 2010 Jan 22;327(5964):469-74
20093474
Nat Genet. 2014 Mar;46(3):305-9
24509479
Genome Res. 2008 May;18(5):821-9
18349386
Nat Genet. 2010 Dec;42(12):1140-3
21037571
Euro Surveill. 2012 Oct 25;17(43):20302
23137466
Lancet. 2013 May 4;381(9877):1551-60
23541540
Euro Surveill. 2013 Mar 07;18(10):20417
23515061
Nat Genet. 2013 Jul;45(7):784-90
23749189
BMC Genomics. 2015 Aug 26;16:637
26306795
Nature. 2011 Aug 24;477(7365):462-5
21866102
Mol Biol Evol. 2012 Aug;29(8):1969-73
22367748
Nucleic Acids Res. 2012 Jan;40(1):e6
22064866
Eur J Clin Microbiol Infect Dis. 2013 Aug;32(8):1017-22
23430195
Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269-73
291943
Eur J Clin Microbiol Infect Dis. 2012 Aug;31(8):2017-28
22278293
BMC Microbiol. 2013 Dec 24;13:302
24364868
BMC Bioinformatics. 2015 Mar 12;16:79
25888166
Lancet Infect Dis. 2014 Oct;14(10):1011-21
24970283
Genome Res. 2008 Mar;18(3):431-41
18256241
BMC Genomics. 2011 Nov 01;12:536
22044686
J Infect Dis. 2002 Jul 1;186(1):127-8
12089674
Cell Microbiol. 2006 Aug;8(8):1228-40
16882028
Nat Genet. 2012 Sep;44(9):1056-9
22863732
Eur J Clin Microbiol Infect Dis. 2009 Jul;28(7):781-91
19156453
Nucleic Acids Res. 2015 Feb 18;43(3):e15
25414349
Microbiology. 2000 Jun;146 ( Pt 6):1345-59
10846213
J Clin Pathol. 1980 Dec;33(12):1179-83
7451664
Clin Infect Dis. 1998 Feb;26(2):502-3
9502483
PLoS Genet. 2013;9(9):e1003741
24039595
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6738-43
24753569
N Engl J Med. 2016 Feb 4;374(5):497-8
26840151
PLoS One. 2011 Mar 03;6(3):e17570
21408607
Bioinformatics. 2011 Feb 15;27(4):578-9
21149342
Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9924-9
15998735