In 2016, an outbreak of invasive Group A Streptococcus (iGAS) infections caused by a rare M protein gene (emm) subtype, emm26.3, was identified in Alaska, USA. We used whole-genome sequencing (WGS) analysis to describe relatedness of outbreak cases and to characterize genomic features of these iGAS isolates.
Case definition: isolation of GAS emm26.3 from a normally sterile site in an Alaska resident from February to November 2016. Paired-end, 250-bp WGS was performed using a MiSeq platform on 32 case isolates. Short reads were assembled using VelvetOptimiser2.2.5. Single Nucleotide Polymorphisms (SNPs) were called from assemblies using kSNP3.0. Reads were also analyzed by an in-house bioinformatics pipeline to detect important gene features.
The 32 case isolates differed, on average, by 2 SNPs (range, 0-6) based on a total of 16 SNP loci across approximately 1.7M-bp shared genome. Four sets of isolates were genomically indistinguishable (n=2, 5, 13, and 3) and were correlated with temporal/geographic groups of cases. Five independent SNPs (all non-synonymous) were located in the regulator operon covRS. Eleven SNPs (7 non-synonymous) affected 11 other genes. Pipeline analysis identified identical gene features across all isolates, including pilus type T28, MLST type ST745, no detectable resistance genes, and positive for genes hasA, prtf2, sfb1, smeZ, speC, and speG.
WGS analysis confirmed the clonal nature of an emm26.3 iGAS disease outbreak, revealing likely transmission clusters. Within the outbreak lineage, virulence regulator covRS showed a disproportionately high number of mutations, which might be partially responsible for increased pathogenicity.