1332. Population structure and genomic analysis of pediatric Streptococcus pyogenes clinical isolates in the United States, 2020 – 2022

Abstract Background Streptococcus pyogenes (GAS) is the major cause of bacterial pharyngitis in children. GAS can cause conditions ranging from asymptomatic pharyngeal carriage to invasive infection. We compared the genomic characteristics of GAS pharyngeal and invasive isolates from U.S. children. Methods We cultured GAS from throat swabs collected from children aged 3–18 years with acute GAS pharyngitis, diagnosed by rapid antigen or molecular test, and from a convenience sample of asymptomatic children during 1/2020 to 3/2022 in Chicago, IL; Atlanta, GA; Portland, OR; Phoenix, AZ. We collected invasive isolates in Chicago. Whole-genome sequencing (WGS) was performed on the Illumina MiSeq for species confirmation, isolate typing, and virulence and antimicrobial gene identification. Reference-based read alignment was used for whole genome phylogenetic analysis. Results Of 1144 collected throat swabs, 684 were from children with pharyngitis and 460 from asymptomatic children. 13 invasive GAS isolates were collected. GAS were cultured from 359 pharyngitis and 20 asymptomatic swabs. Of these, 371 GAS isolates could be recovered and underwent WGS. Thirty isolates (8%) were either low-quality sequences and/or identified as species other than S. pyogenes and were excluded. Whole-genome phylogenetic analysis of 341 GAS (215 pharyngitis, 13 asymptomatic, 13 invasive) identified 25 related clusters and 8 singletons (Figure 1). Virulence gene complements within given emm types were generally concordant with recently published CDC strain data. The most frequently identified resistance genes were tetM and ermB. 281 isolates (82%) carried no antibiotic resistance genes. Some clusters were significantly more represented at certain sites within apparent geographically defined clusters of nearly indistinguishable isolates (Figure 1): cluster 1 in Chicago, emm type 3; cluster 14 in Phoenix and Portland, emm 28, 12; and cluster 15 in Atlanta, emm 89. No major genomic factors were significantly associated with asymptomatic vs pharyngitis vs invasive presentation. Figure 1:Whole genome phylogenetic tree of pediatric GAS isolates Maximum likelihood phylogenetic analysis based on whole-genome alignment of 371 Group A Streptococcus isolates. Tip colors represent cluster assignments based on genetic similarity. Inner ring represents geographic location of GAS isolation. Outer ring represents patient presentation: asymptomatic colonization, symptomatic pharyngitis, or invasive infection. Conclusion Pharyngeal and invasive GAS in children within individual clonal complexes are co-included in closely related clusters, with evidence of close transmission within individual sites Disclosures All Authors: No reported disclosures.