Seasonal, Geographic, and Temporal Trends of emm Clusters Associated With Invasive Group A Streptococcal Infections in US Multistate Surveillance

Smeesters, Pierre; Laho, Delphine; Beall, Bernard; Steer, Andrew C.; Beneden, Chris C.A. Van

doi:10.1093/cid/ciw807

Cited by 28 publications

(17 citation statements)

References 10 publications

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“…(or pattern E) strain cases were disproportionally represented in the summer (third quarter, from July to September) (15). Figure 6 shows that the seasonal relationship of emm clustering (or emm locus patterns) is reflected by the presence or absence of an active sof determinant.…”

Section: Resultsmentioning

confidence: 99%

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Chochua

Metcalf

et al. 2017

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Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3). Sixty-four M protein gene (emm) types were identified among 69 clonal complexes (CCs), including one CC of Streptococcus dysgalactiae subsp. equisimilis. emm types predicted the presence or absence of active sof determinants and were segregated into sof-positive or sof-negative genetic complexes. Only one "emm type switch" between strains was apparent. sof-negative strains showed a propensity to cause infections in the first quarter of the year, while sof ϩ strain infections were more likely in summer. Of 1,454 isolates, 808 (55.6%) were Pnga3 positive and 637 (78.9%) were accounted for by types emm1, emm89, and emm12. Theoretical coverage of a 30-valent M vaccine combined with an M-related protein (Mrp) vaccine encompassed 98% of the isolates. WGS data predicted that 15.3, 13.8, 12.7, and 0.6% of the isolates were nonsusceptible to tetracycline, erythromycin plus clindamycin, erythromycin, and fluoroquinolones, respectively, with only 19 discordant phenotypic results. Close phylogenetic clustering of emm59 isolates was consistent with recent regional emergence. This study revealed strain traits informative for GAS disease incidence tracking, outbreak detection, vaccine strategy, and antimicrobial therapy.IMPORTANCE The current population-based WGS data from GAS strains causing invasive disease in the United States provide insights important for prevention and control strategies. Strain distribution data support recently proposed multivalent M type-specific and conserved M-like protein vaccine formulations that could potentially protect against nearly all invasive U.S. strains. The three most prevalent clonal complexes share key polymorphisms in the nga operon encoding two secreted virulence factors (NADase and streptolysin O) that have been previously associated with high strain virulence and transmissibility. We find that Streptococcus pyogenes is phylogenetically subdivided into loosely defined multilocus sequence type-based clusters consisting of solely sof-negative or sof-positive strains; with sof-negative strains demonstrating differential seasonal preference for infection, consistent with the recently demonstrated differential seasonal preference based on phylogenetic clustering of full-length M proteins. This might relate to the differences in GAS strain com-

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Section: Resultsmentioning

confidence: 99%

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Chochua

Metcalf

et al. 2017

mBio

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114

183

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“…Fluctuations in emm -type distribution have been attributed to multiple factors, such as different frequencies of the most prevalent circulating clones, influence of the herd immunity, different clinical manifestations of iGAS infections associated with specific emm types, age, racial, and seasonal differences ( 25 , 28 , 32 ). Recently, seasonal, geographic, and temporal trends of specific emm clusters associated with iGAS infections have been found, due to a probable different capacity for transmission or infection ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalent emm Types among Invasive GAS in Europe and North America since Year 2000

Gherardi

Vitali

Creti

2018

Front. Public Health

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BackgroundStreptococcus pyogenes or group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections, from uncomplicated to more severe and invasive diseases with high mortality and morbidity. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern; for this purpose the M protein gene (emm) gene typing is the most widely used genotyping method, with more than 200 emm types recognized. Molecular epidemiological data have been also used for the development of GAS M protein-based vaccines.MethodsThe aim of this paper was to provide an updated scenario of the most prevalent GAS emm types responsible for invasive infections in developed countries as Europe and North America (US and Canada), from 1st January 2000 to 31st May 2017. The search, performed in PubMed by the combined use of the terms (“emm”) and (“invasive”) retrieved 264 articles, of which 38 articles (31 from Europe and 7 from North America) met the inclusion criteria and were selected for this study. Additional five papers cited in the European articles but not retrieved by the search were included.Resultsemm1 represented the dominant type in both Europe and North America, replaced by other emm types in only few occasions. The seven major emm types identified (emm1, emm28, emm89, emm3, emm12, emm4, and emm6) accounted for approximately 50–70% of the total isolates; less common emm types accounted for the remaining 30–50% of the cases. Most of the common emm types are included in either one or both the 26-valent and 30-valent vaccines, though some well-represented emm types found in Europe are not.ConclusionThis study provided a picture of the prevalent emm types among invasive GAS (iGAS) in Europe and North America since the year 2000 onward. Continuous surveillance on the emm-type distribution among iGAS infections is strongly encouraged also to determine the potential coverage of the developing multivalent vaccines.

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“…Genomic sequencing has also revealed that certain historically established emm types have been assigned to sequences located in emm-like genes due to the annealing of emm-typing primers to emm-like genes (9). A more recent classification, called the emm-clustertyping scheme, groups strains into 48 clusters based on full M protein sequence homology and functional properties (10)(11)(12).…”

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Analysis of Global Collection of Group A Streptococcus Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins

Frost

Davies

Delforge

et al. 2020

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The core Mga (multiple gene activator) regulon of group A Streptococcus (GAS) contains genes encoding proteins involved in adhesion and immune evasion. While all GAS genomes contain genes for Mga and C5a peptidase, the intervening genes encoding M and M-like proteins vary between strains. The genetic make-up of the Mga regulon of GAS was characterized by utilizing a collection of 1,688 GAS genomes that are representative of the global GAS population. Sequence variations were examined with multiple alignments, and the expression of all core Mga regulon genes was examined by quantitative reverse transcription-PCR in a representative strain collection. In 85.2% of the sampled genomes, the Mga locus contained genes encoding Mga, Mrp, M, Enn, and C5a peptidase proteins. These isolates account for 53% of global infections. Only 9.1% of genomes did not contain either an mrp or an enn gene. The pairwise identity within Enn (68.6%) and Mrp (83.2%) protein sequences was higher than within M proteins (44.7%). Gene expression varied between strains tested, but high expression was recorded for all genes in at least one strain. Previous nomenclature issues were clarified with molecular gene definitions. Our findings support a shift in focus in the GAS research field to further consider the role of Mrp and Enn in virulence and vaccine development. IMPORTANCE While the GAS M protein has been the leading vaccine target for decades, the bacteria encode many other virulence factors of interest for vaccine development. In this work, we show that emm-like genes are encoded in a remarkable majority of GAS genomes and expressed at a level similar to that for the emm gene. In collaboration with the U.S. Centers for Disease Control, we developed molecular definitions of the different emm and emm-like gene families. This clarification should abrogate mistyping of strains, especially in the area of whole-genome typing. We have also updated the emm-typing collection by removing emm-like gene sequences and provided in-depth analysis of Mrp and Enn protein sequence structure and diversity.

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Seasonal, Geographic, and Temporal Trends of emm Clusters Associated With Invasive Group A Streptococcal Infections in US Multistate Surveillance

Cited by 28 publications

References 10 publications

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015

Prevalent emm Types among Invasive GAS in Europe and North America since Year 2000

Analysis of Global Collection of Group A Streptococcus Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins

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