A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development

Martina Sanderson-Smith, David M.P. De Oliveira, Julien Guglielmini, David J. McMillan, Therese Vu, Jessica K. Holien, Anna Henningham, Andrew C. Steer, Debra E. Bessen, James B. Dale, Nigel Curtis, Bernard W. Beall, Mark J. Walker, Michael W. Parker, Jonathan R. Carapetis, Laurence Van Melderen, Kadaba S. Sriprakash, Pierre R. Smeesters*, Michael Batzloff, Rebecca TowersHerman Goossens, Surhbi Malhotra-Kumar, Luiza Guilherme, Rosangela Torres, Donald Low, Allison McGeer, Paula Krizova, Sawsan El Tayeb, Joe Kado, Mark Van Der Linden, Guliz Erdem, Alon Moses, Ran Nir-Paz, Tadayoshi Ikebe, Haruo Watanabe, Samba Sow, Boubou Tamboura, Bard Kittang, José Melo-Cristino, Mario Ramirez, Monica Straut, Alexander Suvorov, Artem Totolian, Mark Engel, Bongani Mayosi, Andrew Whitelaw, Jessica Darenberg, Birgitta Henriques Normark, Chuan Chiang Ni, Jiunn Jong Wu, Aruni De Zoysa, Androulla Efstratiou, Stanford Shulman, Robert Tanz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

257 Citations (Scopus)

Abstract

Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development.

Original languageEnglish
Pages (from-to)1325-1338
Number of pages14
JournalJournal of Infectious Diseases
Volume210
Issue number8
DOIs
Publication statusPublished - 15 Oct 2014

Bibliographical note

Publisher Copyright:
© The Author 2014.

Keywords

  • Epidemiology
  • Fibrinogen
  • IgA
  • IgG
  • M protein
  • Molecular typing
  • Plasminogen
  • Streptococcus pyogenes
  • Vaccine

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