Community outbreaks of group A Streptococcus revealed by genome sequencing

Abstract

The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region. Detailed clinical information was obtained for closely related clusters of isolates. Genomic sequence data was contextualised through comparison with international data. We identified 18 different emm genotypes within our bacterial population, and revealed both highly diverse and closely related isolates. This high level of diversity was maintained even in the context of international sequence data. We also identified two emm1 clusters, and one emm3 cluster, of closely-related isolates that differed only by 1 to 4 single nucleotide polymorphisms. Analysis of clinical information identified no healthcare associated contact between patients, indicating cryptic community transmission. Our findings suggest that genomic surveillance of GAS would increase detection of transmission and highlight opportunities for intervention.

The emergence of successfulStreptococcus pyogeneslineages through convergent pathways of capsule loss and recombination directing high toxin expression

“…We compared the ∼67bp nga-ifs-slo promoter region of the 344 BSAC collection isolate genomes to identify different variants. We expanded the data analysed by including assembled genome data from over 5000 isolates representing 54 different emm types: from Cambridge University Hospital (CUH) (11), the rest of England and Wales collected by Public Health England (PHE) in 2014/2015 (PHE-2014/15) (12, 13) and from the USA collected by the Active Bacterial Core Surveillance System (ABCs) in 2015 (ABCs-2015) (14). We excluded 39 emm -types represented by fewer than 3 isolates (Supplementary Table 2).…”

“…As well as recombination around the P- nga-ifs-slo region, the emergent ST101 variant of emm 89 had also undergone recombination surrounding the hasABC locus, and, in place of the hasABC genes, was a region of 156bp that was not found in genotypes with the capsule locus but is found in the acapsular emm 4 and emm 22 isolates (3). To identify any similar events in other genotypes, we examined the sequences of hasA , hasB, and hasC in the assemblies of isolates from the BSAC collection as well as CUH (11), PHE-2014/15 and ABCs-2015 collections for gene presence as well as premature stop codon mutations or missing genes (Figure 5). The hasABC locus was absent in the majority of emm 89 isolates, consistent with the previous observations describing the recent emergence of the acapsular emm 89 variant (3).…”

“… (A) Maximum likelihood phylogeny constructed with core SNPs following mapping of all available emm 28 genome data to the emm 28 MGAS6180 reference genome (white square) (18). Modern UK isolates (red circles); BSAC (n=15), CUH (n=13 (11)) and PHE-2014/15 (n=240 (12, 13)), one historical English isolate from 1938 (brown circle). North American isolates (blue circles); ABCs-2015 (n=95 (14)), Canada (2011-2013, n=4 (42)), and completed genome strain HarveyGAS (USA, 2017 (43)).…”

“…( B) Regions of recombination were then identified within the emm 28 genome alignment and removed before reconstructing the phylogenetic tree ( C ) Maximum likelihood phylogeny constructed with core SNPs following mapping of all available emm 87 genome sequence data to the reference emm 87 strain NGAS743 (Canada, white circle (48)). UK isolates (red circles); BSAC (2001-2011, n=22), CUH (2008, n=1 (11)), PHE-2014/15 (n=64, (12, 13)). North American isolates (blue circles); ABCs-2015 (n=26, (14)), Canada (n=26, (48)), Texas Children’s Hospital (2012-2016, n=27, (49)).…”

“… (A) Maximum likelihood phylogeny constructed with core SNPs following mapping of all available emm 75 genome sequence data to the French strain STAB090229 (white circle) (50). Modern UK collections (red circles); BSAC (n=11), CUH (n=6 (11)), PHE-2014/15 (n = 141, (12, 13)) and two English historical isolates (brown circles) from 1937/1938. North American isolates (blue circles); ABCs-2015 (n=20, (14)), NGAS344 and NGAS604 from Canada 2011/2012 (42).…”