Evidence for early circulation of the M1UK sublineage of Streptococcus pyogenes in Germany, 2015-2023.

BACKGROUND: Several European countries have reported a rise in invasive Group A Streptococcus (GAS) infections, particularly linked to the toxigenic emm1 sublineage M1UK. In Germany, historical molecular data are limited due to the absence of systematic molecular surveillance. METHODS: We performed whole-genome sequencing (WGS) on 189 invasive Streptococcus pyogenes isolates collected between January 1, 2015, and May 31, 2023, at University Medical Center Carl Gustav Carus, TU Dresden. Clinical data were extracted from patient records. M1UK sublineage identification was based on 27 characteristic single nucleotide polymorphisms (SNPs). A Bayesian coalescent analysis estimated the evolutionary timescales of the M1UK clade in Germany. RESULTS: The most common emm type was emm1 (34%, 64/189), followed by emm12, emm4, and emm89. Of the 64 emm1 isolates, 31 (48%) were M1UK. No significant associations were found between clinical outcomes and M1UK or M1global genotypes. Although a post-pandemic shift favouring M1UK was observed, our analysis indicates that M1UK had already been circulating in Germany by 2017. The estimated most recent common ancestor dates to 2012 (95% highest posterior density: 2009-2015), with a stable effective population size over time. CONCLUSION: Our findings confirm the pre-pandemic circulation of M1UK in Germany. While the clinical impact of M1UK remains unclear, integrating clinical data with high-resolution molecular surveillance may improve early detection of emerging high-risk clones.