Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

What comes after M Conservation of the core Mga regulon of Group A streptococcus (#38)

Hannah RC Frost 1 2 , Mark Davies 3 , Martina Sanderson-Smith 4 , Andrew C Steer 5 6 , Anne Botteaux 2 , Mark J Walker 7 , Pierre R Smeesters 2 8
  1. ULB, Brussels, BRUSSELS, Belgium
  2. Bacterology moleculaire, Universite Libre de Bruxelles, Brussels, Belgium
  3. Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
  4. Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia
  5. Group A Streptococcus Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
  6. Centre for International Child Health, University of Melbourne, Melbourne, Victoria, Australia
  7. Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  8. Department of Pediatrics, Academic Children Hospital Queen Fabiola, Brussels, Belgium

Background: Numerous regulatory systems of Group A streptococcus (GAS) allow adaption to various host environments, enabling infections in diverse human tissues. Mga (multiple gene activator) regulates transcription of up to 10% of the GAS genome, particularly during acute phases of infection. The core Mga regulon contains genes encoding proteins involved in adhesion and evasion of immune responses including the M protein and the M-like proteins Mrp and Enn.

Methods: The genetic make-up of the core Mga regulon of GAS was characterised utilising a collection of over 1400 GAS genomes containing 132 emm-types and 42 emm-clusters, collected from multiple continents and various clinical manifestations. Precise annotation of all core Mga genes has been undertaken and sequence variations were examined with MUSCLE alignments.

Results: In 89% of genomes the locus contained genes mga, mrp, emm, enn and scpa encoding Mga, Mrp, M, Enn and C5a peptidase proteins respectively, in the stated order. Only 8.6% of genomes had emm but neither mrp nor enn genes, and 58% of these also contained a gene for Sic or Protein H. The average pairwise identity within Enn and Mrp proteins was 70% and 81.2% respectively, which is much higher than within M proteins (52.6%).

Conclusions: The Mga regulon in most GAS strains encodes Mrp, M and Enn proteins, suggesting a paradigm shift from M-centric to more inclusive studies. The role of these  M-like proteins should therefore be investigated in more details including the regulation of their expression together with their vaccine potential.