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; M Protein Study Group

doi:10.1093/infdis/jiu260

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

J Infect Dis. 2014 Oct 15;210(8):1325-38. doi: 10.1093/infdis/jiu260. Epub 2014 May 5.

Authors

Martina Sanderson-Smith¹, David M P De Oliveira¹, Julien Guglielmini², David J McMillan³, Therese Vu⁴, Jessica K Holien⁵, Anna Henningham⁶, Andrew C Steer⁷, Debra E Bessen⁸, James B Dale⁹, Nigel Curtis¹⁰, Bernard W Beall¹¹, Mark J Walker⁶, Michael W Parker¹², Jonathan R Carapetis¹³, Laurence Van Melderen¹⁴, Kadaba S Sriprakash¹⁵, Pierre R Smeesters¹⁶; M Protein Study Group

Collaborators

Affiliations

¹ Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Australia.
² Microbial Evolutionary Genomics, Département Génomes et Génétique, Institut Pasteur CNRS, UMR3525, Paris, France.
³ 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.
⁴ 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.
⁵ Biota Structural Biology Laboratory, ACRF Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Melbourne.
⁶ School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane.
⁷ Murdoch Children Research Institute Centre for International Child Health, The University of Melbourne Department of General Medicine, Royal Children's Hospital Melbourne, Australia.
⁸ Department of Microbiology and Immunology, New York Medical College, Valhalla.
⁹ 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.
¹⁰ Murdoch Children Research Institute Infectious Diseases Unit, Royal Children's Hospital Melbourne Department of Paediatrics, The University of Melbourne, Australia.
¹¹ Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.
¹² 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.
¹³ Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth.
¹⁴ Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium.
¹⁵ Bacterial Pathogenesis Laboratory, QIMR Berghofer Medical Research Institute, Brisbane.
¹⁶ 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.

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.

Keywords: IgA; IgG; M protein; Streptococcus pyogenes; epidemiology; fibrinogen; molecular typing; plasminogen; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cloning, Molecular
Gene Expression Regulation, Bacterial*
Molecular Sequence Data
Phylogeny
Recombinant Proteins
Streptococcal Vaccines / immunology*
Streptococcus pyogenes / classification*
Streptococcus pyogenes / physiology*

Substances

Bacterial Proteins
Recombinant Proteins
Streptococcal Vaccines

Grants and funding

R01 AI010085/AI/NIAID NIH HHS/United States