Emergent Invasive Group A Streptococcus dysgalactiae subsp. equisimilis, United States, 2015-2018

Abstract

The term group A Streptococcus is considered synonymous for the species Streptococcus pyogenes. We describe an emergent invasive S. dysgalactiae subspecies equisimilis lineage that obtained the group A antigen through a single ancestral recombination event between a group C S. dysgalactiae subsp. equisimilis strain and a group A S. pyogenes strain.

Keywords: ABCs; Active Bacterial Core surveillance; GAS; Lancefield group A antigen; Streptococccus equisimilis; Streptococcus dysgalactiae; Streptococcus pyogenes; bacteria; bacterial infections; invasive group A Streptococcus; multilocus sequence type; streptococci.

Figure 1

Analyses of invasive group A Streptococcus dysgalactiae subspecies equisimilis and conserved genomic pepD gene insertion site of highly related exotoxin speC gene–containing prophages found within group A ST128 S. equisimilis strain and S. pyogenes strain SP1336. Methods are described in the Appendix. A) Phylogenetic tree of 35 invasive group A S. dysgalactiae subsp. equisimilis (GAS/SE/MLST128 [ST128] complex) isolates and 13 unrelated group C, G, and L SE isolates recovered through the Centers for Disease Control and Prevention’s Active Bacterial Core surveillance during January 1, 2015–November 1, 2018. Trees are drawn to scale; branch lengths indicate number of substitutions per site. Surveillance areas (https://www.cdc.gov/abcs/reports-findings/surv-reports.html) are indicated: EB, East Bay San Francisco area, California; NY, New York; NM, New Mexico; CA, San Francisco Bay area, California; OR, Oregon; CO, Colorado; GA, Georgia; CT, Connecticut. Different counties and years of isolation are indicated (e.g., EB1–15 indicates county 1 in East Bay area and year 2015). The left tree depicts all 49 isolates and the right includes only the subset of the 36 GAS/ST128/SE (also including GAS/ST128/SE described by Brandt et al. [3] and assigned GenBank accession no. HE858529). Three pairs of isolates differing by 13 or fewer single-nucleotide polymorphisms are shown in red. Single-locus variants of the indicated multilocus sequence types are indicated with asterisks. B) Conserved genomic pepD gene insertion site of highly related exotoxin speC gene–containing prophages found within group A ST128 S. equisimilis strain (middle) and S. pyogenes strain SP1336 (GenBank accession no. CP031738). The nonfunctional pepD structural genes lacking bases 1–4 are depicted in the 2 prophage-containing strains. Nucleotide sequence identity is scaled from 70% (yellow) to 100% (green). The S. equisimilis prophage also contained the virulence-associated DNase gene spd1 as shown and previously described for the depicted SP1336 phage shown (8). Within both species, the pepD insertion site lies within a region between the conserved bacterial cell division genes ftsE/ftsX and the small ribosomal protein gene rpsL31b (GenBank accession no. for S. equisimilis AC2713 is HE858529).

Figure 2

Ancestral recombination event depicting Streptococcus pyogenes group A carbohydrate gene donor (GAS/SP-5005; GenBank accession no. NC007297), group C S. dysgalactiae subsp. equisimilis recipient (GCS/SE7136; GenBank accession no. NCTC7136), and progeny group A S. dysgalactiae subsp. equisimilis progeny (GAS/SE/ST128) described in study of emergent invasive group A Streptococcus dysgalactiae subspecies equisimilis, United States, 2015–2018. The deduced crossover points between the group A gene cluster (red) donor and group C (green) recipient strains are shown. The 3 genes required for inclusion of the immunodominant N-acetylglucosamine side chain within the group A carbohydrate (gacI, gacJ, and gacK) are shown in red. The coordinates of the fragment transferred that is highly conserved between the donor and the progeny are indicated. The length of the 3 genomic regions are indicated. The gacE/gccE and ebsA genes are shown as green/red hybrids. The extra gcc cluster genes not conserved within the gac cluster are shown in blue. The relative sequence identities of the 3 different regions of progeny (bottom) gac cluster genes with the group A S. pyogenes donor (top) and group C S. equisimilis recipient (middle) are indicated. The middle segment (asterisk) indicates a range of 56%–77% sequence identity between each of the 8 structural genes (gacF–pepT) that were received intact from the S. pyogenes donor. The gac cluster genes are described in more detail in van Sorge et al. (1). Gene assignments are as follows: dnaG, DNA primase; rpoD, major RNA polymerase sigma factor; mscF, metal sulfur complex assembly factor; gacA-L, group A carbohydrate biosynthetic genes (putative functions described in van Sorge et al. [1]); gccA-N, group C carbohydrate biosynthetic genes. gccA-L are functional homologs of gacA-L. gccM and gccN putatively encode an additional glycosyl transferase and UDP-monosaccharide 4-epimerase, respectively; ebsA, pore-forming protein; fd, ferredoxin (complement strand); ctlK, cytidylate kinase; infC, translation initiation factor IF-3.