title: A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.
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.
authors.affiliation: Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Australia.
authors.forename: Martina
authors.initials: M
authors.lastname: Sanderson-Smith
authors.affiliation: Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Australia.
authors.forename: David M P
authors.initials: DM
authors.lastname: De Oliveira
authors.affiliation: Microbial Evolutionary Genomics, Département Génomes et Génétique, Institut Pasteur CNRS, UMR3525, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Guglielmini
authors.affiliation: Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Brisbane Inflammation and Healing Research Cluster, School of Health and Sports Sciences, University of the Sunshine Coast, Sippy Downs, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: McMillan
authors.affiliation: Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Brisbane Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Therese
authors.initials: T
authors.lastname: Vu
authors.affiliation: Biota Structural Biology Laboratory, ACRF Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Melbourne.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Holien
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane.
authors.forename: Anna
authors.initials: A
authors.lastname: Henningham
authors.affiliation: Murdoch Children Research Institute Centre for International Child Health, The University of Melbourne Department of General Medicine, Royal Children's Hospital Melbourne, Australia.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Steer
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla.
authors.forename: Debra E
authors.initials: DE
authors.lastname: Bessen
authors.affiliation: Department of Medicine, The University of Tennessee Health Science Center Department of Veterans Affairs Medical Center, and Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis.
authors.forename: James B
authors.initials: JB
authors.lastname: Dale
authors.affiliation: Murdoch Children Research Institute Infectious Diseases Unit, Royal Children's Hospital Melbourne Department of Paediatrics, The University of Melbourne, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
authors.affiliation: Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Beall
authors.affiliation: School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Walker
authors.affiliation: Biota Structural Biology Laboratory, ACRF Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Melbourne Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Carapetis
authors.affiliation: Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Van Melderen
authors.affiliation: Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Brisbane.
authors.forename: Kadaba S
authors.initials: KS
authors.lastname: Sriprakash
authors.affiliation: Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium Murdoch Children Research Institute.
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Smeesters
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D010802:Phylogeny; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000145:classification* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines
keywords: IgA; IgG; M protein; Streptococcus pyogenes; epidemiology; fibrinogen; molecular typing; plasminogen; vaccine