Poster Presentation Lorne Infection and Immunity 2014

A new paradigm for the systematic and functional classification of Streptococcus pyogenes (#204)

Martina Sanderson-Smith 1 , David De Oliveira 1 , Julien Guglielmini 2 , David McMillan 3 , Therese Vu 3 , Jessika Holien 4 , Anna Henningham 5 , Andrew Steer 6 , Debra Bessen 7 , James Dale 8 , Nigel Curtis 6 , Bernard Beall 9 , Mark Walker 5 , Michael Parker 4 , Jonathan Carapetis 10 , Laurence Van Melderen 11 , Kadaba Sriprakash 3 , Pierre Smeesters 6 11
  1. Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia
  2. Microbial Evolutionary Genomics, Département Génomes et Génétique, Institut Pasteur, Paris, France
  3. Bacterial Pathogenesis Laboratory, Queensland Institute of Medical Research, Brisbane, QL, Australia
  4. Biota Structural Biology Laboratory, ACRF Rational Drug Discovery Centre. St. Vincent's Institute of Medical Research, Melbourne, Vic, Australia
  5. School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QL, Australia
  6. Murdoch Childrens Research Institute, PARKVILLE, VIC, Australia
  7. Department of Microbiology and Immunology, New York Medical College, Valhalla, USA
  8. Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, USA
  9. Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, USA
  10. Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, Australia
  11. Laboratoire de Génétique et Physiologie Bactérienne, Institut de Biologie et de Médecine Moléculaires, Faculté des Sciences, Université Libre de Bruxelles, Gosselies, Belgium

Streptococcus pyogenes is responsible for more than 500,000 deaths per year and ranks amongst 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 surface M protein is the major virulence factor of Streptococcus pyogenes. The protein has numerous binding partners and these interactions assist the bacteria in evading host immune responses. The M protein is also used as the substrate for epidemiological typing and is the main vaccine candidate. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development.

A worldwide comprehensive study of 1086 GAS isolates collected from 31 countries representing 175 M-types was used to investigate the feasibility and value of a new typing system.

A functional classification based on 48 clusters containing closely related M proteins that share adaptive evolution patterns is proposed. The cluster classification correlates the function of the 26 representative M proteins to 5 of the most important host ligands described to date. The classification system is also concordant with binding motifs defined by computational modelling for an additional 119 M proteins. Cluster classification is therefore likely to be of biological relevance and may provide insights into clinically relevant aspects of M protein function. The need for a paradigm shift from type-specific immunity against Streptococcus pyogenes to cluster-based immunity for this bacterium should be further investigated.

In conclusion, our work proposes a new typing system for Streptococcus pyogenes that will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance and vaccine development.