Emergence of a New Highly Successful Acapsular Group A Streptococcus Clade of Genotype emm89 in the United Kingdom.

Claire E Turner,Theresa Lamagni,Laurence Game,Matthew T G Holden,Androulla Efstratiou,Shiranee Sriskandan,James Abbott,Michael D Jones,Sophia David,Paul Stephen Keim

doi:10.1128/mbio.00622-15

Claire E Turner, Theresa Lamagni + Show 8 more

Open Access

https://doi.org/10.1128/mbio.00622-15

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Abstract

ABSTRACTGroup A Streptococcus (GAS) genotype emm89 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 emm89 invasive GAS disease in the United Kingdom, prompting longitudinal investigation of this genotype. Whole-genome sequencing revealed a recent dramatic shift in the emm89 population with the emergence of a new clade that increased to dominance over previous emm89 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 emm89 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 emm89 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 emm89 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 emm12 and modern emm1 strains but different from the rest of the sequenced emm89 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 emm89 variants and may explain the changes observed in emm89 GAS epidemiology.

Highlights

IMPORTANCE Sudden upsurges or epidemic waves are common features of group A streptococcal disease
We hypothesize that the genome remodeling that occurred in the emergent clade variant provided a selective advantage that allowed it to outcompete other emm89 variants
A high level of variation can occur within specific emm-type populations, but this is usually attributed to mobile genetic element-mediated DNA transfer such as bacteriophages or integrative conjugative elements (ICEs)

Summary

Introduction

IMPORTANCE Sudden upsurges or epidemic waves are common features of group A streptococcal disease. We identified a new clade variant that had recently emerged in the emm population after having undergone several core genomic recombination-related changes, two of which affected known virulence factors. Observed upsurges in GAS disease are associated with the emergence and expansion of a new emm genotype or the sudden increase of a preexisting common emm type. The mechanisms behind such epidemic waves of disease are largely unknown but may in part be due to the transference of new virulence factors between strains, mediated by mobile genetic elements such as bacteriophages commonly found in the GAS population. The emergent acapsular clade variant increased in the population, temporally associated with the rise in emm iGAS, and is the dominant emm variant in the United Kingdom population

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