Evidence map›Paper›PMID 24733896›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences.

Waleed Nasser, Stephen B Beres, Randall J Olsen, Melissa A Dean, Kelsey A Rice, S Wesley Long, Karl G Kristinsson, Magnus Gottfredsson, Jaana Vuopio, Kati Raisanen and 9 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed
38.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

169 citing papers in PubMed, 266 citations in OpenAlex.

  1. Tracing the recent evolution of Group AEmerging microbes & infections · 2026
    Review
  2. Genomic analysis of Streptococcus pyogenes emm1-type isolates reveals M1European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  3. Article
  4. Evaluating the use of whole-genome sequencing and SangerJournal of medical microbiology · 2026
    Article
  5. Article
  6. Observational
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  8. Analysis ofmBio · 2025
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  16. Review
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109 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 11 institutions in 7 countries.

Waleed NasserCenter for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX 77030.
Stephen B Beres
Randall J Olsen
Melissa A Dean
Kelsey A Rice
S Wesley Long
Karl G Kristinsson
Magnus Gottfredsson
Jaana Vuopio
Kati Raisanen
Dominique A Caugant
Martin Steinbakk
Donald E Low
Allison McGeer
Jessica Darenberg
Birgitta Henriques-Normark
Chris A Van Beneden
Steen Hoffmann
James M Musser
Houston Methodist · USMethodist Hospital · USMount Sinai Hospital · CANorwegian Institute of Public Health · NOUniversity of Turku · FIKarolinska University Hospital · SENational Center for Immunization and Respiratory Diseases · USNational University Hospital of Iceland · ISPublic Health Agency of Sweden · SEStatens Serum Institut · DKUniversity of Iceland · IS

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.

Indexed as

EpidemicsEvolution, MolecularAnimalsBase SequenceDisease Models, AnimalFasciitis, NecrotizingFinlandGenes, BacterialGenome, BacterialGenomicsHumansINDEL MutationPharyngitisPolymorphism, Single NucleotidePrimatesSelection, Geneticflesh-eating diseasemobile genetic elementmolecular clockpathogenesisphylogeography

Identifiers

PMID24733896
PMCPMC4035937
OpenAlexW1989769331

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.