Abstract

Plain Language Summary Background: An increased incidence of group A Streptococcus -related scarlet fever has been observed in Shanghai since 2011, characterized by the co-circulation of both emm 12 and emm 1 strains. The comparative virulence potential of these two dominant strains, which is critical for understanding their dynamics and severity, remains largely under researched. This study aimed to systematically compare their virulence determinants to uncover the molecular basis for their successful dissemination. Methods: As the dominant strains that cause scarlet fever, 16 isolates each of both emm 1 and emm 12 were selected from the Children’s Hospital at Fudan University between 2011 and 2022 using a stratified random sampling method. We compared the two strain types in terms of the positivity rate of virulence factors, adherence and internalization capacity into epithelial cells, biofilm formation capacity, and resistance to innate immune responses. Results: Genomic analysis revealed significant divergence between the emm 1 and emm 12 strains, particularly within the Fibronectin-Collagen-T antigen (FCT) region and fibronectin-binding protein and superantigen genes. These genetic differences were reflected in functionally distinct phenotypes. Emm 1 strains (linked to FCT2) exhibited a superior colonization capacity, demonstrating rates of epithelial cell adherence and internalization that were approximately two-folds higher, and significantly enhanced biofilm formation compared to emm 12 strains (linked to FCT4; P < 0.05). Furthermore, emm 1 strains showed significantly greater resistance to innate immune clearance, with higher survival rates in human whole blood, serum, and phagocytic cells ( P < 0.001). Conclusions: The enhanced in vitro colonization and immune evasion fitness of emm 1 strains are likely attributable to their distinct virulence gene repertoir