Abstract

A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001–2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406. Analysis of the whole genome SNP-based phylogeny showed that the majority of isolates from the 2008–2009 upsurge period belonged to a distinct lineage characterized by the presence of a prophage carrying the speC exotoxin and spd1 DNAase genes but loss of two other prophages considered typical of the emm/M3 lineage. This lineage was significantly associated with the upsurge in iGAS cases and we postulate that the upsurge could be attributed in part to expansion of this novel prophage-containing lineage within the population. The study underlines the importance of prompt genomic analysis of changes in the GAS population, providing an advanced public health warning system for newly emergent, pathogenic strains.

Highlights

  • Group A Streptococcus (GAS) has long been recognized as a human pathogen responsible for a diverse range of diseases

  • Novel lineage containing a prophage in emm/M3 group A Streptococcus wide collection of isolates was used as a sampling frame to randomly select 200 GAS emm/M3 strains as part of this study, 160 from 2008/2009 and 40 isolates from the previous period of enhanced surveillance, January 2003 to December 2004

  • To determine if emm/M3 isolates from the invasive Group A Streptococcus (iGAS) upsurge period (November 2008 to April 2009) were distinct in any way, the genomes of 447 emm/M3 isolates, including 60 from the upsurge period, were sequenced

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Summary

Introduction

Group A Streptococcus (GAS) has long been recognized as a human pathogen responsible for a diverse range of diseases. GAS infections cause significant morbidity and mortality globally, largely attributable to rheumatic heart disease and invasive infection. The minimum estimate, of over 500 000 deaths per year, places GAS among the major human pathogens (Carapetis et al, 2005). The organism itself possesses numerous surface-associated and secreted proteins that play a key role in host–bacteria interaction such as adherence and immune evasion (Bisno et al, 2003; Cunningham, 2000) and are subject to strong selective pressure.

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