Detection of Streptococcus pyogenes M1UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

Mark R Davies; Nadia Keller; Stephan Brouwer; Magnus G Jespersen; Amanda J Cork; Andrew J Hayes; Miranda E Pitt; David M P De Oliveira; Nichaela Harbison-Price; Olivia M Bertolla; Daniel G Mediati; Bodie F Curren; George Taiaroa; Jake A Lacey; Helen V Smith; Ning-Xia Fang; Lachlan J M Coin; Kerrie Stevens; Steven Y C Tong; Martina Sanderson-Smith; Jai J Tree; Adam D Irwin; Keith Grimwood; Benjamin P Howden; Amy V Jennison; Mark J Walker

doi:10.1038/s41467-023-36717-4

Detection of Streptococcus pyogenes M1_UK in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA

Nat Commun. 2023 Feb 24;14(1):1051. doi: 10.1038/s41467-023-36717-4.

Authors

Mark R Davies^#¹, Nadia Keller^#², Stephan Brouwer^#², Magnus G Jespersen^#³, Amanda J Cork², Andrew J Hayes³, Miranda E Pitt³, David M P De Oliveira², Nichaela Harbison-Price², Olivia M Bertolla², Daniel G Mediati⁴, Bodie F Curren², George Taiaroa³, Jake A Lacey⁵, Helen V Smith⁶, Ning-Xia Fang⁶, Lachlan J M Coin³, Kerrie Stevens⁷, Steven Y C Tong^{5

8}, Martina Sanderson-Smith⁹, Jai J Tree⁴, Adam D Irwin^{10

11}, Keith Grimwood^{12

13}, Benjamin P Howden⁷, Amy V Jennison⁶, Mark J Walker¹⁴

Affiliations

¹ Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. mark.davies1@unimelb.edu.au.
² Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences and Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
³ Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁴ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
⁵ Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁶ Public Health Microbiology, Queensland Health Forensic and Scientific Services, Queensland Health, Coopers Plains, QLD, Australia.
⁷ 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.
⁸ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁹ Illawarra Health and Medical Research Institute and Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia.
¹⁰ University of Queensland Centre for Clinical Research, Brisbane, QLD, Australia.
¹¹ Queensland Children's Hospital, 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 Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences and Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. mark.walker@uq.edu.au.

^# Contributed equally.

Abstract

A new variant of Streptococcus pyogenes serotype M1 (designated 'M1_UK') 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 'M1_global' and M1_UK 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 M1_UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1_UK 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 M1_UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance.

Publication types

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

MeSH terms

Australia
Bacterial Proteins / genetics
Exotoxins / genetics
Humans
Mutation
Scarlet Fever* / epidemiology
Streptococcal Infections*
Streptococcus pyogenes / genetics
Superantigens
United Kingdom

Substances

Superantigens
Bacterial Proteins
Exotoxins