Predominance of M1UK type strains and their clinical impact in invasive Streptococcus pyogenes infections in Japan, 2023–2025

<title>Abstract</title> <p> Purpose The clinical relevance of M1 _UK type strains of <italic>Streptococcus pyogenes</italic> in Japan remains insufficiently defined. We investigated the molecular epidemiology of M1 _UK type strains and evaluated their clinical impact among adults with invasive group A <italic>Streptococcus</italic> (iGAS) infections. Methods We conducted a nationwide multicenter surveillance study of iGAS infections from December 2023 to March 2025. Molecular typing, profiling of M1 _UK -associated single-nucleotide polymorphisms (SNPs), and <italic>emm</italic> -cluster assignment were performed. Adult clinical characteristics and outcomes were compared between M1 _UK type and non-M1 _UK type infections after exclusion of the single adult M1 _global case. Results Among 155 patients in the molecular epidemiology cohort, M1 _UK type strains accounted for 58 isolates, comprising M1 _UK subtype ( <italic>rofA</italic> -only) (n = 25) and M1 _UK (n = 33) strains, whereas M1 _global was rare (n = 1). Historical analysis suggested a shift from early M1 _global predominance toward recent detection of M1 _UK subtype ( <italic>rofA</italic> -only) and M1 _UK strains. In adult clinical comparisons, M1 _UK type infection was associated with streptococcal toxic shock syndrome (STSS; <italic>p</italic>  = 0.004) and necrotizing fasciitis ( <italic>p</italic>  &lt; 0.001). In multivariable analysis, younger age, necrotizing fasciitis, and serum creatinine ≥ 2.0 mg/dL were associated with M1 _UK type infection. Conclusion M1 _UK type strains were important contributors to contemporary iGAS infections in Japan and were associated with severe clinical presentations, supporting sustained molecular surveillance beyond conventional <italic>emm</italic> typing. </p>