Abstract

BackgroundStreptococcus pyogenes is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies.MethodsWe used whole-genome sequencing (WGS) to characterize all invasive S. pyogenes isolates obtained through the United States Center for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including emm type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within emm type.ResultsSeventy-one emm types were identified from 3873 isolates characterized. The emm types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of emm types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the erm-positive emm types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three emm types (emm 49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup (P-values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages.ConclusionsWhile the overall population structure of invasive S. pyogenes isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections.

Highlights

  • Group A Streptococcus (GAS) is a Gram-positive bacterium that causes a variety of diseases in humans

  • We included 3,873 (99.4%) isolates identified as S. pyogenes; 22 non-S. pyogenes GAS isolates were excluded

  • A total of 71 emm types were identified among the 3,864 isolates (9 isolates were non-typeable)

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Summary

Introduction

Group A Streptococcus (GAS) is a Gram-positive bacterium that causes a variety of diseases in humans. Invasive GAS (iGAS) infections are associated with high case fatality ratios. The introduction of a novel or rare strain into a population has repeatedly been demonstrated to cause a rise in Streptococcus pyogenes infections (Tyrrell et al, 2010; Turner et al, 2015; Mosites et al, 2018), and key genomic changes within relatively uncommon strains that affect virulence factor structure or expression have been associated with subsequent global expansion (Turner et al, 2015; Beres et al, 2016). Understanding iGAS disease trends and associated strain features through surveillance increases the understanding of population dynamics of GAS and can guide development of effective prevention strategies. Streptococcus pyogenes is a major cause of severe, invasive infections in humans. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies

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