Insights gained from sequencing Australian non- invasive and invasive Streptococcus pyogenes isolates

Epidemiological data have indicated that invasive infections caused by the Gram- positive cocci Streptococcus pyogenes (group A streptococcus, GAS) have increased in many Australian states over the past two decades. In July 2022, invasive GAS (iGAS) infections became nationally notifiable in Australia via public- health agencies. Surveillance for S. pyogenes infections has been sporadic within the state of New South Wales (NSW). This has led to a lack of genetic data on GAS strains in circulation, particularly for non- invasive infections, which are the leading cause of GAS's burden on the Australian healthcare system. To address this gap, we used whole- genome sequencing to analyse the genomes of 318 S. pyogenes isolates collected within two geographical regions of NSW. Invasive isolates were collected in 2007-2017, whilst non- invasive isolates were collected in 2019-2021. We found that at least 66 different emm- types were associated with clinical disease within NSW. There was no evidence of any Australian- specific clones in circulation. The M1UK variant of the emm1 global pandemic clone (M1global) has been detected in our isolates from 2013 onwards. We detected antimicrobial- resistance genes (mainly tetM, ermA or ermB genes) in less than 10 % of our 318 isolates, which were more commonly associated with non- invasive infections. Superantigen virulence gene carriage was reasonably proportionate between non- invasive and invasive infection isolates. Our study adds rich data on the genetic makeup of historical S. pyogenes infections within Australia. Ongoing surveillance of invasive and non- invasive GAS infections within NSW by whole- genome sequencing is warranted to inform on outbreaks, antimicrobial resistance and vaccine coverage.