Epidemiological and Molecular Characterization of an Invasive Group A Streptococcus emm 32.2 Outbreak

Abstract

An emm32.2 invasive group A streptococcus (iGAS) outbreak occurred in Liverpool from January 2010 to September 2012. This genotype had not previously been identified in Liverpool, but was responsible for 32% (14/44) of all iGAS cases reported during this time period. We performed a case-case comparison of emm32.2 iGAS cases with non-emm32.2 control iGAS cases identified in the Liverpool population over the same time period to assess patient risk factors for emm32.2 iGAS infection. The emm32.2 iGAS cases were confined to the adult population. We show that homelessness, intravenous drug use, and alcohol abuse predisposed patients to emm32.2 iGAS disease; however, no obvious epidemiological linkage between the patients with emm32.2 iGAS could be identified. Comparative whole-genome sequencing analysis of emm32.2 iGAS and non-emm32.2 control isolates was also performed to identify pathogen factors which might have driven the outbreak. We identified 19 genes, five of which had previously been implicated in virulence, which were present in all of the emm32.2 iGAS isolates but not present in any of the non-emm32.2 control isolates. We report that a novel emm32.2 genotype emerged in Liverpool in 2010 and identified a specific subset of genes, which could have allowed this novel emm32.2 genotype to persist in a disadvantaged population in the region over a 3-year period.

Keywords: Streptococcus pyogenes; accessory genome; antibiotic resistance; comparative genomics; epidemiological data; iGAS; molecular epidemiology; phylogeny; streptococci; virulence factors; whole-genome sequencing.

FIG 1

Histogram plot of all iGAS cases in Liverpool from January 2010 to December 2012 reported to the Respiratory and Vaccine Preventable Bacteria Reference Unit of Public Health England. Over this time period, 14 outbreak emm32.2 outbreak iGAS cases were reported.

FIG 2

Maximum likelihood phylogeny of the 48 GAS isolates based on core genome SNPs. Each branch is annotated with the isolate source followed by the in silico emm type. R, the GAS reference sequence Streptococcus pyogenes HKU16; C, control iGAS cases; N, control noninvasive isolates; and O, outbreak emm32.2 iGAS cases. (Right) The absence (gray) or presence (black) of accessory genes in each strain in no particular order. An expanded version of this figure, showing the gene names is presented in Table S1 in the supplemental material.

FIG 3

Maximum likelihood phylogeny of the 48 GAS isolates based on core genome SNPs. Each branch is annotated with isolate source followed by the in silico emm type. R, the GAS reference sequence Streptococcus pyogenes HKU16; C, control iGAS cases; N, control noninvasive isolates; and O, outbreak emm32.2 iGAS cases. (Middle) Antibiotic resistance and superantigen genes (in gray) in the genomes of the study isolates. (Right) Predicted genomic locations of putative prophage elements in each study isolate.