title: Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline.
abstract: Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates.
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.|Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Violette
authors.initials: V
authors.lastname: Da Cunha
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 15A, UK.|Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072 Queensland, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Davies
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Douarre
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rosinski-Chupin
authors.affiliation: Novartis Vaccines and Diagnostics, Siena 53100, Italy.
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
authors.affiliation: Centre National de Référence des Streptocoques, Hôpitaux Universitaires, Paris Centre Cochin-Hôtel Dieu-Broca, Paris 75014, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Spinali
authors.affiliation: Novartis Vaccines and Diagnostics, Siena 53100, Italy.
authors.forename: Tim
authors.initials: T
authors.lastname: Perkins
authors.affiliation: Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lechat
authors.affiliation: Centre National de Référence des Streptocoques, Hôpitaux Universitaires, Paris Centre Cochin-Hôtel Dieu-Broca, Paris 75014, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dmytruk
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sauvage
authors.affiliation: Institut Pasteur Genomic platform, Paris 75015, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ma
authors.affiliation: Novartis Vaccines and Diagnostics, Siena 53100, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Romi
authors.affiliation: Institut Pasteur Genomic platform, Paris 75015, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Tichit
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Lopez-Sanchez
authors.affiliation: Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Descorps-Declere
authors.affiliation: Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Souche
authors.affiliation: CNRS UMR3525, Paris 75015, France.|Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris 75015, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS ERL3526, Paris 75015, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
authors.affiliation: Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Moszer
authors.affiliation: Institut Pasteur, Collection de l'Institut Pasteur (CIP), Paris 75015, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Clermont
authors.affiliation: Novartis Vaccines and Diagnostics, Siena 53100, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Maione
authors.affiliation: Institut Pasteur Genomic platform, Paris 75015, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, 7006 Queensland, Australia.|Inflammation and Healing Research Cluster, University of the Sunshine Coast, Sippy Downs, 4556 Queensland, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: McMillan
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 15A, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Novartis Vaccines and Diagnostics, Siena 53100, Italy.
authors.forename: John L
authors.initials: JL
authors.lastname: Telford
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 15A, UK.
authors.forename: Gordan
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072 Queensland, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 15A, UK.
authors.forename: Matthew T G
authors.initials: MTG
authors.lastname: Holden
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|Centre National de Référence des Streptocoques, Hôpitaux Universitaires, Paris Centre Cochin-Hôtel Dieu-Broca, Paris 75014, France.|Institut Cochin, Université Sorbonne Paris Descartes, Paris 75014, France.|INSERM, U1016, Paris 75014, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.affiliation: Institut Pasteur, Unité de Biologie des Bacteries Pathogènes à Gram-positif, Paris 75015, France.|CNRS UMR3525, Paris 75015, France.|Institut Pasteur, Bioinformatics platform, Paris 75015, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Glaser
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D002999:Clone Cells; D004251:DNA Transposable Elements; D005060:Europe / Q000453:epidemiology; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D009656:North America / Q000453:epidemiology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013290:Streptococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013752:Tetracycline / Q000494:pharmacology*; D013753:Tetracycline Resistance / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements; D013752:Tetracycline
references.citation: J Antimicrob Chemother. 2009 Sep;64(3):441-6
references.pmid: 19608582
references.citation: Nat Rev Microbiol. 2012 Mar 16;10(4):266-78
references.pmid: 22421879
references.citation: PLoS Biol. 2006 May;4(5):e88
references.pmid: 16683862
references.citation: Microbiol Mol Biol Rev. 2010 Sep;74(3):417-33
references.pmid: 20805405
references.citation: Eur J Clin Microbiol Infect Dis. 2012 Sep;31(9):2301-10
references.pmid: 22358726
references.citation: Front Microbiol. 2013 Mar 06;4:15
references.pmid: 23508522
references.citation: Acta Vet Scand. 2011 Feb 08;53:4
references.pmid: 21299911
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Vet Microbiol. 2013 Jan 25;161(3-4):286-94
references.pmid: 22964008
references.citation: Antimicrob Agents Chemother. 1998 Sep;42(9):2312-8
references.pmid: 9736555
references.citation: Nat Commun. 2013;4:2151
references.pmid: 23877117
references.citation: Bioinformatics. 2013 Aug 15;29(16):1970-9
references.pmid: 23766415
references.citation: J Clin Microbiol. 2008 Apr;46(4):1285-91
references.pmid: 18287314
references.citation: Dtsch Med Wochenschr. 1965 Feb 5;90:258-61
references.pmid: 14237948
references.citation: Bacteriol Rev. 1976 Sep;40(3):774-92
references.pmid: 791241
references.citation: J Clin Microbiol. 2011 Oct;49(10):3652-5
references.pmid: 21865428
references.citation: J Med Microbiol. 2007 Jul;56(Pt 7):947-955
references.pmid: 17577061
references.citation: J Exp Med. 2010 Oct 25;207(11):2313-22
references.pmid: 20956545
references.citation: mBio. 2010 Aug 24;1(3):
references.pmid: 20824105
references.citation: J Clin Microbiol. 2003 Jun;41(6):2530-6
references.pmid: 12791877
references.citation: BMC Bioinformatics. 2013 Sep 22;14:277
references.pmid: 24053737
references.citation: BMC Genomics. 2013 Jul 24;14:500
references.pmid: 23879707
references.citation: Cell Mol Life Sci. 2010 Feb;67(3):419-31
references.pmid: 19862477
references.citation: Mol Biol Evol. 2012 Aug;29(8):1969-73
references.pmid: 22367748
references.citation: J Antimicrob Chemother. 2010 Sep;65(9):1907-14
references.pmid: 20584746
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13950-5
references.pmid: 16172379
references.citation: BMC Evol Biol. 2007 Nov 08;7:214
references.pmid: 17996036
references.citation: mBio. 2013 Aug 20;4(4):
references.pmid: 23963180
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15961-6
references.pmid: 18832470
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12391-6
references.pmid: 12200547
references.citation: Genome Res. 2008 May;18(5):821-9
references.pmid: 18349386
references.citation: J Med Microbiol. 2012 Jan;61(Pt 1):126-131
references.pmid: 21903822
references.citation: BMC Genomics. 2008 Feb 08;9:75
references.pmid: 18261238
references.citation: Mol Microbiol. 1998 Apr;28(1):103-17
references.pmid: 9593300
references.citation: mBio. 2013 Dec 17;4(6):e00889-13
references.pmid: 24345744
references.citation: mBio. 2012 Jul 17;3(4):e00151-12
references.pmid: 22807567
references.citation: J Clin Microbiol. 2005 Aug;43(8):3727-33
references.pmid: 16081902
references.citation: Nat Genet. 2013 Jan;45(1):109-13
references.pmid: 23222960
references.citation: Lancet. 2012 Feb 11;379(9815):547-56
references.pmid: 22226047
references.citation: BMC Genomics. 2013 Apr 15;14:252
references.pmid: 23586779
references.citation: J Clin Microbiol. 2009 Mar;47(3):800-3
references.pmid: 19109468
references.citation: Genome Res. 2004 Jul;14(7):1394-403
references.pmid: 15231754
references.citation: J Med Microbiol. 2012 Aug;61(Pt 8):1109-1113
references.pmid: 22538994
references.citation: Eur J Clin Microbiol Infect Dis. 2012 Aug;31(8):1741-7
references.pmid: 22120421
references.citation: N Engl J Med. 1964 Dec 10;271:1221-8
references.pmid: 14234266
references.citation: Appl Environ Microbiol. 2010 Dec;76(24):7957-65
references.pmid: 20952646
references.citation: J Clin Microbiol. 2005 Dec;43(12):5899-906
references.pmid: 16333073
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60 ; second page, table of contents
references.pmid: 11381101
references.citation: Clin Microbiol Rev. 2005 Jan;18(1):102-27
references.pmid: 15653821
references.citation: FEMS Microbiol Rev. 2011 Sep;35(5):856-71
references.pmid: 21658082
references.citation: MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1-36
references.pmid: 21088663
references.citation: J Clin Microbiol. 2009 Apr;47(4):1143-8
references.pmid: 19158264
references.citation: Mol Microbiol. 2002 Sep;45(6):1499-513
references.pmid: 12354221
references.citation: Science. 2011 Jan 28;331(6016):430-4
references.pmid: 21273480
references.citation: Mol Biol Evol. 2012 Sep;29(9):2157-67
references.pmid: 22403239