Emergence of a New Highly Successful Acapsular Group A
Streptococcus
Clade of Genotype
emm
89 in the United Kingdom
Authors: Turner Claire E. , Abbott James , Lamagni Theresa , Holden Matthew T. G. , David Sophia , Jones Michael D. , Game Laurence , Efstratiou Androulla , Sriskandan Shiranee 
Published: July 2015

Group A
Streptococcus
(GAS) genotype
emm
89 is increasingly recognized as a leading cause of disease worldwide, yet factors that underlie the success of this
emm
type are unknown. Surveillance identified a sustained nationwide increase in
emm
89 invasive GAS disease in the United Kingdom, prompting longitudinal investigation of this genotype. Whole-genome sequencing revealed a recent dramatic shift in the
emm
89 population with the emergence of a new clade that increased to dominance over previous
emm
89 variants. Temporal analysis indicated that the clade arose in the early 1990s but abruptly increased in prevalence in 2008, coinciding with an increased incidence of
emm
89 infections. Although standard variable typing regions (
emm
subtype,
tee
type,
sof
type, and multilocus sequence typing [MLST]) remained unchanged, uniquely the emergent clade had undergone six distinct regions of homologous recombination across the genome compared to the rest of the sequenced
emm
89 population. Two of these regions affected known virulence factors, the hyaluronic acid capsule and the toxins NADase and streptolysin O. Unexpectedly, and in contrast to the rest of the sequenced
emm
89 population, the emergent clade-associated strains were genetically acapsular, rendering them unable to produce the hyaluronic acid capsule. The emergent clade-associated strains had also acquired an NADase/streptolysin O locus nearly identical to that found in
emm
12 and modern
emm
1 strains but different from the rest of the sequenced
emm
89 population. The emergent clade-associated strains had enhanced expression of NADase and streptolysin O. The genome remodeling in the new clade variant and the resultant altered phenotype appear to have conferred a selective advantage over other
emm
89 variants and may explain the changes observed in
emm
89 GAS epidemiology.

IMPORTANCE
Sudden upsurges or epidemic waves are common features of group A streptococcal disease. Although the mechanisms behind such changes are largely unknown, they are often associated with an expansion of a single genotype within the population. Using whole-genome sequencing, we investigated a nationwide increase in invasive disease caused by the genotype
emm
89 in the United Kingdom. We identified a new clade variant that had recently emerged in the
emm
89 population after having undergone several core genomic recombination-related changes, two of which affected known virulence factors. An unusual finding of the new variant was the loss of the hyaluronic acid capsule, previously thought to be essential for causing invasive disease. A further genomic adaptation in the NADase/streptolysin O locus resulted in enhanced production of these toxins. Recombination-related genome remodeling is clearly an important mechanism in group A
Streptococcus
that can give rise to more successful and potentially more pathogenic variants.