Integrated whole-genome sequencing and temporospatial analysis of a continuing Group A Streptococcus epidemic

Abstract

Analysis of microbial epidemics has been revolutionized by whole-genome sequencing. We recently sequenced the genomes of 601 type emm59 Group A Streptococcus (GAS) organisms responsible for an ongoing epidemic of invasive infections in Canada and some of the United States. The epidemic has been caused by the emergence of a genetically distinct, hypervirulent clone that has genetically diversified. The ease of obtaining genomic data contrasts with the relatively difficult task of translating them into insightful epidemiological information. Here, we sequenced the genomes of 90 additional invasive Canadian emm59 GAS organisms, including 80 isolated recently in 2010–2011. We used an improved bioinformatics pipeline designed to rapidly process and analyze whole-genome data and integrate strain metadata. We discovered that emm59 GAS organisms are undergoing continued multiclonal evolutionary expansion. Previously identified geographic patterns of strain dissemination are being diluted as mixing of subclones over time and space occurs. Our integrated data analysis strategy permits prompt and accurate mapping of the dissemination of bacterial organisms in an epidemic wave, permitting rapid generation of hypotheses that inform public health and virulence studies.

Clinical Laboratory Response to a Mock Outbreak of Invasive Bacterial Infections: a Preparedness Study

“…The 67 emm59 strains differed, on average, by 17 polymorphisms (mean, 15 single-nucleotide polymorphisms [SNPs] and 2 indels; range, 0 to 25 SNPs and 0 to 6 indels). This very low level of sequence diversity is similar to the results from previous investigations of the Canadian emm59 epidemic clone (10)(11)(12)16). Five sets of genomically indistinguishable strains were identified (see Table S1 in the supplemental material), indicating that those infections likely arose from direct human-to-human transmission.…”

“…Three strains were selected using the following criteria: (i) the strains were recovered from patients in Minnesota, since a single state was used to emulate a regional outbreak scenario, and emm59 strains were the most common GAS serotype recovered in Minnesota during the collection dates; (ii) the strains were located on different branches of the phylogenetic tree; and (iii) the strains had the most frequent (wild-type) alleles for all major transcription regulatory genes. A nonrandom overrepresentation of polymorphisms occurring in the regulatory genes CovR-CovS and Mga has been reported in Canadian emm59 strains (12). Among these 67 U.S. strains, 29 had a polymorphism in CovR-CovS or Mga (P Ͻ 0.001 for each gene, chi-square test).…”

“…A review of all publically available emm59 GAS genome sequence data demonstrated that, albeit small, sufficient genetic diversity exists among the strains comprising the epidemic clone used to define distinct subclonal lineages (10)(11)(12). To test the hypothesis that strains recovered in the United States have a nonrandom temporal-spatial distribution, a neighbor-joining tree was constructed.…”

“…Thus, it was a best-case scenario. Serotype emm59 GAS organisms are typically an uncommon cause of human disease (7)(8)(9); however, a hypervirulent clone recently arose, and its progeny spread rapidly throughout Canada, causing many hundreds of severe invasive infections (10)(11)(12). The surveillance data from the Centers for Disease Control and Prevention now indicate that the frequency of emm59 GAS infections is increasing in some areas of the United States, particularly Minnesota (13).…”

High Incidence of Invasive Group A Streptococcus Disease Caused by Strains of Uncommon emm Types in Thunder Bay, Ontario, Canada

“…Beginning in 2006, Canada experienced an epidemic of invasive GAS (iGAS) infections caused by strains of the previously rare emm59 type (5). A hypervirulent clone, which later disseminated to several areas of the United States, was shown to be responsible for hundreds of cases countrywide (6)(7)(8)(9)(10). Invasive type emm59 strains were frequently isolated from soft tissue infections and were recovered in higher percentages from patients with distinctive risk factors, including alcohol abuse, homelessness, hepatitis C virus (HCV) infection, and intravenous drug use (IVDU) (5,6).…”