Evolutionary dynamics and virulence factor variability in invasive <i>Streptococcus pyogenes</i> in Norway, 2017−2023

Invasive infections caused by <i>Streptococcus pyogenes</i> (iGAS) have increased in Europe over the past decade, with a marked upsurge after the COVID-19 pandemic. Here, we examined whether the increase in iGAS infections in Norway was associated with the spread of variants that had acquired new virulence factors. A collection of 1,163 iGAS isolates submitted to the National Reference Laboratory between January 2017 and April 2023, representing 87% of all cases recorded by the Norwegian Surveillance System for Infectious Diseases, was analyzed by whole genome sequencing. Resistance to one or more antibiotics was found in 15.6% of the isolates: 14.1% were resistant to tetracycline, 6.4% to erythromycin, and 4.0% to clindamycin. Resistance to other antibiotics was < 1%. The dominating <i>emm</i> types were <i>emm1</i> (30.9%), <i>emm12</i> (13.8%), <i>emm89</i> (9.3%), <i>emm28</i> (8.3%), <i>emm4</i> (6.0%), and <i>emm87</i> (4.5%), with the remaining isolates belonging to 55 other <i>emm</i> types; 62.3% of <i>emm1</i> belonged to the hypervirulent lineage M1_UK. Genetic characterization of the virulence factors of the dominant six <i>emm</i> types demonstrated extensive competition between related phages, leading to phage switching and interplay between integration and excision of temperate phages carrying virulence factors. Bacteriophages carrying virulence factors <i>speC</i> and <i>spd1</i> displayed a particularly high turnover rate, with several pairs of otherwise genomically identical isolates exhibiting different phage-carrying status. We identified and characterized four new <i>speC</i> and <i>spd1</i>-carrying phages. The rapid turnover pattern of these, as well as other phages carrying superantigens and DNAses suggests an important role in pathogenesis.IMPORTANCEThis analysis of 1,163 iGAS isolates collected between January 2017 and April 2023 aimed to map virulence factor content to understand the observed increased incidence of iGAS in Norway. Our findings indicate that 15.6% of the isolates were resistant to at least one antibiotic, with tetracycline resistance being the most common. The dominant <i>emm</i> types were <i>emm</i>1, <i>emm</i>4, <i>emm</i>12, <i>emm</i>28, <i>emm</i>87, and <i>emm</i>89, which together accounted for 72.7% of the isolates. The study highlights the dynamic nature of virulence factor-carrying temperate phages, particularly the ones carrying <i>speC</i> and <i>spd1</i>, which frequently integrate and excise within <i>emm</i> types. Four previously unseen phages carrying <i>speC</i> and <i>spd1</i> were identified and characterized. This research underscores the complexity of iGAS epidemiology and the need for continuous surveillance to understand the evolving landscape of bacterial virulence factors, antibiotic resistance, and circulating <i>emm</i> types.