Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2023

Detection of Streptococcus pyogenes M1UK in Australia and characterisation of the mutation driving enhanced expression of superantigen SpeA (92818)

Stephan Brouwer 1 2 , Mark R Davies 3 , Nadia Keller 1 , Magnus G Jespersen 3 , Amanda J Cork 1 2 , Andrew J Hayes 3 , Miranda E Pitt 3 , David MP De Oliveira 1 2 , Nichaela Harbison-Price 1 2 , Olivia M Bertolla 1 2 , Daniel G Mediati 4 , Bodie F Curren 1 , George Taiaroa 3 , Jake A Lacey 3 , Helen V Smith 5 , Ning-Xia Fang 5 , Lachlan JM Coin 3 , Kerrie Stevens 6 , Steven YC Tong 7 8 , Martina Sanderson-Smith 9 , Jai J Tree 4 , Adam D Irwin 10 11 , Keith Grimwood 12 13 , Benjamin P Howden 14 , Amy V Jennison 5 , Mark J Walker 1 2
  1. Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  3. Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia
  4. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
  5. Public Health Microbiology, Queensland Health Forensic and Scientific Services, Coopers Plains, QLD, Australia
  6. Microbiological Diagnostic Unit Public Health Laboratory, The Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  7. Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  8. Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  9. Ilawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia
  10. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
  11. Queensland Children’s Hospital, Queensland Government, Brisbane, QLD, Australia
  12. School of Medicine and Dentistry and Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia
  13. Departments of Infectious Diseases and Paediatrics, Gold Coast Health, Gold Coast, QLD, Australia
  14. Microbiological Diagnostic Unit Public Health Laboratory, The Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

A new variant of Streptococcus pyogenes serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.