Skip to main content

Advertisement

SpringerLink
Log in

A clone of the emergent Streptococcus pyogenes emm89 clade responsible for a large outbreak in a post-surgery oncology unit in France

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

An outbreak of nosocomial infections due to Streptococcus pyogenes (Group A Streptococcus; GAS) occurred in a post-surgery oncology unit and concerned more than 60 patients and lasted 20 months despite enhanced infection control and prophylaxis measures. All GAS strains were characterized (emm genotype, toxin gene profile and pulse-field gel electrophoresis subtype). Selected strains were sequenced and phylogenetic relationship established. Capacity to form biofilm and interaction with human pulmonary epithelial cells and macrophages were determined. Twenty-six GAS strains responsible for invasive infections (II) and 57 for non-II or colonization were isolated from patients (n = 66) or healthcare workers (n = 13). Seventy strains shared the same molecular markers and 69 the same PFGE pattern; 56 were sequenced. They all belonged to the emerging emm89 clade 3; all but 1 were clonal. Whole genome sequencing identified 43 genetic profiles with sporadic mutations in regulatory genes and acquired mutations in 2 structural genes. Except for two regulatory gene mutants, all strains tested had the same biofilm formation capacity and displayed similar adherence and invasion of pulmonary epithelial cells and phagocytosis and survival in human macrophages. This large outbreak of GAS infection in a post-surgery oncology unit, a setting that contains highly susceptible patients, arose from a strain of the emergent emm89 clade. No relationship between punctual or acquired mutations, invasive status, and strain phenotypic characteristics was found. Noteworthy, the phenotypic characteristics of this clone account for its emergence and its remarkable capacity to elicit outbreaks.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Carapetis JR, Steer AC, Mulholland EK, Weber M (2005) The global burden of group A streptococcal diseases. Lancet Infect Dis 5:685–694

    Article  Google Scholar 

  2. Deutscher M, Schillie S, Gould C et al (2011) Investigation of a group A streptococcal outbreak among residents of a long-term acute care hospital. Clin Infect Dis 52:988–994

    Article  Google Scholar 

  3. Beall B, Facklam R, Thompson T (1996) Sequencing emm-specific pcr products for routine and accurate typing of group A streptococci. J Clin Microbiol 34:953–958

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Plainvert C, Doloy A, Loubinoux J et al (2012) Invasive group A streptococcal infections in adults, France (2006–2010). Clin Microbiol Infect 18:702–710

    Article  CAS  Google Scholar 

  5. Steer AC, Law I, Matatolu L, Beall BW, Carapetis JR (2009) Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 9:611–616

    Article  Google Scholar 

  6. Nasser W, Beres SB, Olsen RJ et al (2014) Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences. Proc Natl Acad Sci USA 111:E1768–E1776

    Article  CAS  Google Scholar 

  7. Turner CE, Abbott J, Lamagni T et al (2015) Emergence of a new highly successful acapsular group A Streptococcus clade of genotype emm89 in the united kingdom. MBio 6:e00622

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhu L, Olsen RJ, Nasser W, de la Riva Morales I, Musser JM (2015) Trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of emm89 Streptococcus pyogenes. MBio 6:e01378-01315

    Article  Google Scholar 

  9. Friaes A, Machado MP, Pato C, Carrico J, Melo-Cristino J, Ramirez M (2015) Emergence of the same successful clade among distinct populations of emm89 Streptococcus pyogenes in multiple geographic regions. MBio 6:e01780–e01715

    Article  CAS  Google Scholar 

  10. Musser JM, Zhu L, Olsen RJ, Nasser W. Musser et al (2015) Reply to “Emergence of the same successful clade among distinct populations of emm89 Streptococcus pyogenes in multiple geographic regions”. MBio 6:e01838–e01815

    Article  CAS  Google Scholar 

  11. Turner CE, Lamagni T, Holden MT et al Turner et al (2015) Reply to “Emergence of the same successful clade among distinct populations of emm89 Streptococcus pyogenes in multiple geographic regions”. MBio 6:e01883–e01815

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Latronico F, Nasser W, Puhakainen K et al (2016) Genomic characteristics behind the spread of bacteremic group A Streptococcus type emm89 in finland, 2004–2014. J Infect Dis 214:1987–1995

    Article  Google Scholar 

  13. Beres SB, Kachroo P, Nasser W et al (2016) Transcriptome remodeling contributes to epidemic disease caused by the human pathogen Streptococcus pyogenes. MBio 7:e00403–e00416

    Article  Google Scholar 

  14. Beres SB, Olsen RJ, Ojeda Saavedra M et al (2017) Genome sequence analysis of emm89 Streptococcus pyogenes strains causing infections in scotland, 2010–2016. J Med Microbiol 66:1765–1773

    Article  Google Scholar 

  15. Chochua S, Metcalf BJ, Li Z et al (2017) Population and whole genome sequence based characterization of invasive group A streptococci recovered in the united states during 2015. MBio 8:e01422-17

    Article  Google Scholar 

  16. Teatero S, Coleman BL, Beres SB et al (2017) Rapid emergence of a new clone impacts the population at risk and increases the incidence of type emm89 group A Streptococcus invasive disease. Open Forum Infect Dis 4:ofx042

    Article  Google Scholar 

  17. Falkenhorst G, Bagdonaite J, Lisby M et al (2008) Outbreak of group A streptococcal throat infection: don’t forget to ask about food. Epidemiol Infect 136:1165–1171

    Article  CAS  Google Scholar 

  18. Thigpen MC, Thomas DM, Gloss D et al (2007) Nursing home outbreak of invasive group A streptococcal infections caused by 2 distinct strains. Infect Control Hosp Epidemiol 28:68–74

    Article  Google Scholar 

  19. Yang P, Peng X, Yang J, Dong X, Zhang M, Wang Q (2013) A probable food-borne outbreak of pharyngitis after a massive rainstorm in beijing, caused by emm89 group A Streptococcus rarely found in China. Int J Infect Dis 17:e471

    Article  Google Scholar 

  20. Tenover FC, Arbeit RD, Goering RV et al (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33:2233–2239

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Zerbino DR, Birney E. Velvet (2008) Algorithms for de novo short read assembly using de bruijn graphs. Genome Res 18:821–829

    Article  CAS  Google Scholar 

  22. Darling AC, Mau B, Blattner FR, Perna NT. Mauve (2004) Multiple alignment of conserved genomic sequence with rearrangements. Genome Res 14:1394–1403

    Article  CAS  Google Scholar 

  23. Karadjian G, Hassanin A, Saintpierre B et al (2016) Highly rearranged mitochondrial genome in nycteria parasites (haemosporidia) from bats. Proc Natl Acad Sci USA 113:9834–9839

    Article  CAS  Google Scholar 

  24. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    CAS  Google Scholar 

  25. Tamura K, Nei M, Kumar S (2004) Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101:11030–11035

    Article  CAS  Google Scholar 

  26. Tamura K, Kumar S (2002) Evolutionary distance estimation under heterogeneous substitution pattern among lineages. Mol Biol Evol 19:1727–1736

    Article  CAS  Google Scholar 

  27. Kumar S, Stecher G, Tamura K (2016) Mega7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874

    Article  CAS  Google Scholar 

  28. Koller T, Manetti AG, Kreikemeyer B et al (2010) Typing of the pilus-protein-encoding fct region and biofilm formation as novel parameters in epidemiological investigations of Streptococcus pyogenes isolates from various infection sites. J Med Microbiol 59:442–452

    Article  Google Scholar 

  29. Dinis M, Plainvert C, Kovarik P, Longo M, Fouet A, Poyart C (2014) The innate immune response elicited by group A Streptococcus is highly variable among clinical isolates and correlates with the emm type. PLoS One 9:e101464

    Article  Google Scholar 

  30. Milne I, Stephen G, Bayer M et al (2013) Using tablet for visual exploration of second-generation sequencing data. Br Bioinform 14:193–202

    Article  CAS  Google Scholar 

  31. Watanabe S, Sasahara T, Arai N et al (2016) Complete genome sequence of Streptococcus pyogenes strain jmub1235 isolated from an acute phlegmonous gastritis patient. Genome Announc 4:e01133-16

    Article  Google Scholar 

  32. Young C, Holder RC, Dubois L, Reid SD (2016) Streptococcus pyogenes biofilm. In: Ferretti JJ, Stevens DL, Fischetti VA (eds) Streptococcus pyogenes: basic biology to clinical manifestations 2016/02/12 edn

  33. Lembke C, Podbielski A, Hidalgo-Grass C, Jonas L, Hanski E, Kreikemeyer B (2006) Characterization of biofilm formation by clinically relevant serotypes of group A streptococci. Appl Environ Microbiol 72:2864–2875

    Article  CAS  Google Scholar 

  34. Churchward G (2007) The two faces of janus: virulence gene regulation by CovR/S in group A streptococci. Mol Microbiol 64:34–41

    Article  CAS  Google Scholar 

  35. Cho KH, Caparon MG (2005) Patterns of virulence gene expression differ between biofilm and tissue communities of Streptococcus pyogenes. Mol Microbiol 57:1545–1556

    Article  CAS  Google Scholar 

  36. Fiedler T, Koller T, Kreikemeyer B (2015) Streptococcus pyogenes biofilms-formation, biology, and clinical relevance. Front Cell Infect Microbiol 5:15

    Article  Google Scholar 

  37. Courtney HS, Ofek I, Penfound T et al (2009) Relationship between expression of the family of M proteins and lipoteichoic acid to hydrophobicity and biofilm formation in Streptococcus pyogenes. PLoS One 4:e4166

    Article  Google Scholar 

  38. Sugareva V, Arlt R, Fiedler T, Riani C, Podbielski A, Kreikemeyer B (2010) Serotype- and strain-dependent contribution of the sensor kinase CovS of the CovRS two-component system to Streptococcus pyogenes pathogenesis. BMC Microbiol 10:e01133-16

    Article  Google Scholar 

  39. Alam FM, Turner CE, Smith K, Wiles S, Sriskandan S (2013) Inactivation of the CovR/S virulence regulator impairs infection in an improved murine model of Streptococcus pyogenes naso-pharyngeal infection. PLoS One 8:e61655

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Santé Publique France, INSERM, CNRS, Université Paris Descartes and by the High Council for Scientific and Technological Cooperation between France-Israel “Complexity in Biology” program.

Author information

Authors and Affiliations

  1. INSERM, U1016, Institut Cochin, 75014, Paris, France

    Céline Plainvert, Magalie Longo, Benjamin Saintpierre, Frédéric Ariey, Claire Poyart & Agnès Fouet

  2. Université Sorbonne Paris Descartes, 75014, Paris, France

    Céline Plainvert, Magalie Longo, Benjamin Saintpierre, Frédéric Ariey, Claire Poyart & Agnès Fouet

  3. CNRS (UMR 8104), 75014, Paris, France

    Céline Plainvert, Magalie Longo, Benjamin Saintpierre, Frédéric Ariey, Claire Poyart & Agnès Fouet

  4. Assistance Publique Hôpitaux de Paris, Service de Bactériologie, Centre National de Référence des Streptocoques, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, 75014, Paris, France

    Céline Plainvert, Nicolas Dmytruk, Gislène Collobert & Claire Poyart

  5. Centre de Prévention des infections associées aux soins, Assistance Publique Hôpitaux de Paris, 75014, Paris, France

    Elise Seringe & Pascal Astagneau

  6. Unité Ecologie et Evolution de la Résistance aux Antibiotiques, Institut Pasteur, 75724, Paris, France

    Elisabeth Sauvage & Philippe Glaser

  7. CNRS UMR3525, Paris, 75724, France

    Elisabeth Sauvage & Philippe Glaser

  8. Institut Pasteur, Pôle Biomics, 75724, Paris, France

    Laurence Ma

  9. GGIV Unit, Institut Pasteur, 75724, Paris, France

    Johann Beghain

  10. Centre Médical de Forcilles, 77150, Lesigny, France

    Eric Hernandez & Christian Manuel

  11. Faculté de Médecine, APHP, Pitie-Salpétrière, Sorbonne Université, 75013, Paris, France

    Pascal Astagneau

Authors
  1. Céline Plainvert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magalie Longo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elise Seringe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benjamin Saintpierre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisabeth Sauvage
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laurence Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Johann Beghain
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicolas Dmytruk
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gislène Collobert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eric Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christian Manuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pascal Astagneau
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Philippe Glaser
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Frédéric Ariey
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Claire Poyart
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Agnès Fouet
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the study: Céline Plainvert, Agnès Fouet, and Claire Poyart. Provided clinical and epidemiological data Elise Seringe, Eric Hernandez, and Pascal Astagneau. Performed the bacteriological analyses Magalie Longo, Nicolas Dmytruk, and Gislaine Collobert. Performed biofilms and phagocytosis analyses Magalie Longo. Performed whole genome sequencing of bacterial strains Benjamin Saintpierre, Elisabeth Sauvage, Laurence Ma and Johann Beghain. Analyzed genomes data Philippe Glaser, Frédéric Ariey, and Agnès Fouet. Wrote the manuscript Claire Poyart, Céline Plainvert, and Agnès Fouet.

Corresponding author

Correspondence to Claire Poyart.

Ethics declarations

Conflict of interest

The other authors declare no competing financial interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

430_2018_546_MOESM1_ESM.tiff

Figure S1. The outbreak emm89-F isolates form substantial biofilms compared to other non-emm89 GAS strains. A tendency curve was calculated using the means shown in Fig. 4, y = 0.0362 x + 8.8 excluding the mutants in regulatory genes. The sampling year is indicated below. Symbols are the same as in Fig. 1 (TIFF 1521 KB)

Supplementary material 2 (DOCX 56 KB)

Supplementary material 3 (DOCX 23 KB)

Supplementary material 4 (XLSX 26 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Plainvert, C., Longo, M., Seringe, E. et al. A clone of the emergent Streptococcus pyogenes emm89 clade responsible for a large outbreak in a post-surgery oncology unit in France. Med Microbiol Immunol 207, 287–296 (2018). https://doi.org/10.1007/s00430-018-0546-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-018-0546-1

Keywords

Search

Navigation