Poster Presentation BacPath 2024

Molecular characterisation and RT-PCR based diagnosis of the pandemic Streptococcus pyogenes M1UK lineage (#82)

Stephan Brouwer 1 2 , Olivia M Bertolla 1 2 , Magnus G Jespersen 3 , Amanda J Cork 1 2 , Andrew J Hayes 3 , Daniel G Mediati 4 , Jai J Tree 4 , Adam D Irwin 5 6 , Jacob A Tickner 5 6 , Mark R Davies 3 , Mark J Walker 1 2
  1. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, 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. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
  6. Queensland Paediatric Infectious Diseases Sakzewski Laboratory, Centre for Children’s Health Research, Queensland Children’s Hospital, Brisbane, QLD, Australia

Streptococcus pyogenes (Group A Streptococcus, GAS) is a strictly human-adapted pathogen and causative agent of a broad spectrum of diseases accounting for hundreds of millions of infections each year, being a leading cause of infectious disease related deaths worldwide. To date, there are no licensed vaccines for prevention of GAS infection, and the global burden of GAS diseases is widely recognised as a major public health concern1. Recently, a new variant of GAS serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, driving seasonal scarlet fever surges and a marked increase in invasive infections with severe outcomes in children. Rapid global expansion and clonal replacement of the progenitor GAS ‘M1global’ genotype by this newly emergent M1UK variant is a global public health threat warranting increased surveillance. M1UK differs from M1global by 27 single nucleotide polymorphisms (SNPs) and is characterised by increased expression of the superantigen SpeA in vitro. Here, we report a previously unappreciated mechanism of toxin regulation whereby a single SNP in the 5’ transcriptional leader sequence of the transfer-messenger RNA gene ssrA is responsible for increased transcriptional read-through in M1UK, driving increased expression of the downstream adjacent speA superantigen gene2. This discovery led to the development of an allele-specific real-time PCR assay targeting the ssrA SNP for the detection of M1UK strains. The assay was evaluated using a panel of 51 clinical isolates comprising different emm types and showed very high specificity and sensitivity3. Our study establishes the M1UK-specific ssrA SNP as a suitable target for efficient and rapid identification of M1UK isolates and presents a powerful, cost-effective molecular tool to help support global surveillance efforts of toxigenic M1UK.

  1. Brouwer S, Rivera-Hernandez T, Curren BF, et al. Pathogenesis, epidemiology and control of Group A Streptococcus infection. Nat Rev Microbiol 2023; 21(7): 431-47.
  2. Davies MR, Keller N, Brouwer S, et al. Detection of Streptococcus pyogenes M1(UK) in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA. Nat Commun 2023; 14(1): 1051. 3.
  3. Brouwer S, Swairindhree D, Hayes AJ, et al. A rapid molecular detection tool for toxigenic M1UK Streptococcus pyogenes. J Infect Dis 2024; Aug 29:jiae437: online ahead of print.