Type 2 diabetes mellitus wake-up call: fatal streptococcal toxic shock syndrome triggered by the M1(UK) Streptococcus pyogenes - a case report with genomic insights.

INTRODUCTION: Streptococcus pyogenes (S. pyogenes) can cause streptococcal toxic shock syndrome (STSS), especially in immunocompromised individuals. Early diagnosis is the key to treat STSS effectively. This study presents a fatal case of STSS caused by the emerging M1(UK) S. pyogenes lineage in a patient with type 2 diabetes mellitus (T2DM), alongside a comprehensive literature review. CASE PRESENTATION: A 65-year-old man with T2DM presented with altered consciousness, necrotizing soft tissue injury and was diagnosed with STSS. Bacterial cultures were obtained from right lower limb exudate, right hand mass pus and scrotal pus. Antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS), phylogenomic analysis, and virulence profiling were performed. S. pyogenes isolates from all sites were identified as M1(UK) (emm1/ST28) lineage, closely related to UK strains. The strain was resistant to tetracycline, erythromycin, and clindamycin (ermB, tetM, lmrP) but remained susceptible to β-lactams. Key virulence genes included slo, speC/speG, hasABC and scpA. The slo-mediated endothelial lysis and speC/G-induced cytokine storm contributed to capillary leakage and rapid clinical deterioration. Increased hasABC-mediated capsule expression under hyperglycemia further impaired bacterial clearance. CONCLUSION: This case highlights the threat of antimicrobial-resistant M1(UK) S. pyogenes in patient with T2DM. The pathogenicity of strain was driven by cytolytic toxins, superantigens, and immune evasion. Early STSS diagnosis is facilitated by microscopic examination and rapid antigen detection test (RADT) of group A streptococcus. CLINICAL TRIAL NUMBER: Not applicable.