ArticleThe Journal of clinical investigation2015
A molecular trigger for intercontinental epidemics of group A Streptococcus.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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.
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.
Who cites it
93 citing papers in PubMed, 136 citations in OpenAlex.
- Tracing the recent evolution of Group AEmerging microbes & infections · 2026Review
- Sudden re-emergence ofNew microbes and new infections · 2026Article
- Emergence of clade 3Microbiology (Reading, England) · 2025Article
- Analysis ofmBio · 2025Article
- Identifying genetic variations ineLife · 2025Article
- Integrating Deep Learning Models with Genome-Wide Association Study-Based Identification Enhanced Phenotype Predictions in Group AJournal of microbiology and biotechnology · 2025Article
- Article
- Article
- Epidemiology of Streptococcus pyogenes upper respiratory tract infections in Poland (2003-2017).Journal of applied genetics · 2024Article
- Molecular characterization ofMicrobial genomics · 2024Article
- EmergentInfection and immunity · 2024Article
- Outbreak ofMicrobiology spectrum · 2024Article
- The germ theory revisited: A noncentric view on infection outcome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Epidemiology and emm types among group A streptococcal pharyngitis in Finland: a prospective laboratory-based study.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Interplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability.Nature communications · 2023Article
- Pathogenesis, epidemiology and control of Group A Streptococcus infection.Nature reviews. Microbiology · 2023Review
- Elucidation of independently modulated genes inmSystems · 2023Article
- Structural basis underlying the synergism of NADase and SLO during group A Streptococcus infection.Communications biology · 2023Article
- Genomic epidemiology ofFrontiers in microbiology · 2023Article
- Genome-Wide Transposon Mutagenesis Screens Identify Group A Streptococcus Genes Affecting Susceptibility to β-Lactam Antibiotics.Journal of bacteriology · 2022Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The identification of the molecular events responsible for strain emergence, enhanced virulence, and epidemicity has been a long-pursued goal in infectious diseases research. A recent analysis of 3,615 genomes of serotype M1 group A Streptococcus strains (the so-called "flesh-eating" bacterium) identified a recombination event that coincides with the global M1 pandemic beginning in the early 1980s. Here, we have shown that the allelic variation that results from this recombination event, which replaces the chromosomal region encoding secreted NADase and streptolysin O, is the key driver of increased toxin production and enhanced infection severity of the M1 pandemic strains. Using isoallelic mutant strains, we found that 3 polymorphisms in this toxin gene region increase resistance to killing by human polymorphonuclear leukocytes, increase bacterial proliferation, and increase virulence in animal models of pharyngitis and necrotizing fasciitis. Genome sequencing of an additional 1,125 streptococcal strains and virulence studies revealed that a highly similar recombinational replacement event underlies an ongoing intercontinental epidemic of serotype M89 group A Streptococcus infections. By identifying the molecular changes that enhance upper respiratory tract fitness, increased resistance to innate immunity, and increased tissue destruction, we describe a mechanism that underpins epidemic streptococcal infections, which have affected many millions of people.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.