ArticleNature communications2014
A random six-phase switch regulates pneumococcal virulence via global epigenetic changes.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
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Who cites it
166 citing papers in PubMed.
- Epidemiological characteristics of nasopharyngeal Streptococcus pneumoniae strains among children with pneumonia in Chongqing, China.Scientific reports · 2019Trial
- Type I restriction-modification systems regulate gene expression through DNA topology.Nucleic acids research · 2026Article
- Article
- Quantitative analysis of bacterial cell-cell communication at the single-cell level using microdroplet arrays.Communications biology · 2026Article
- Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.Cell host & microbe · 2026Article
- Epigenetic regulation in prokaryotes: transcriptional and phenotypic outcomes of DNA methyltransferase activity.FEMS microbiology reviews · 2026Review
- Genomics of Irish swine-derivedMicrobial genomics · 2026Article
- The metabolic, microbial and immunological demands of pneumococcal colonisation.PLoS pathogens · 2025Review
- Chromosomal Curing Drives an Arms Race Between Bacterial Transformation and Prophage.Molecular biology and evolution · 2025Article
- Mechanisms of 10-hydroxyoctadecanoic acid resistance inJournal of bacteriology · 2025Article
- Long read metagenomics-based precise tracking of bacterial strains and genomic changes after fecal microbiota transplantation.bioRxiv : the preprint server for biology · 2025Article
- Streptococcus pneumoniae synchronizes the states of cell wall peptidoglycan acetylation and genome methylation by programmed DNA inversions.PLoS pathogens · 2025Article
- Pore-C sequencing identifies episome-driven chromosome conformation perturbations differentiating pneumococcal epigenetic variants.PLoS pathogens · 2025Article
- Deep-learning of Nanopore sequences reveals the 6mA distribution and dynamics in human gut microbiome.National science review · 2025Article
- Streptococcus pneumoniae epidemiology, pathogenesis and control.Nature reviews. Microbiology · 2025Review
- Decoding Adenine DNA Methylation Effects in Streptococcus Mutans: Insights Into Self-DNA Protection and Autoaggregation.Molecular oral microbiology · 2025Article
- 100+ years of phase variation: the premier bacterial bet-hedging phenomenon.Microbiology (Reading, England) · 2025Review
- Influence of Aging and Immune Alterations on Susceptibility to Pneumococcal Pneumonia in the Elderly.Pathogens (Basel, Switzerland) · 2025Review
- PneumoBrowse 2: an integrated visual platform for curated genome annotation and multiomics data analysis of Streptococcus pneumoniae.Nucleic acids research · 2025Article
- Decoding the genome and epigenome of avianFrontiers in veterinary science · 2025Article
106 more citing papers are in PubMed but not listed here.
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18 authors.
Funding
Abstract
Streptococcus pneumoniae (the pneumococcus) is the world's foremost bacterial pathogen in both morbidity and mortality. Switching between phenotypic forms (or 'phases') that favour asymptomatic carriage or invasive disease was first reported in 1933. Here, we show that the underlying mechanism for such phase variation consists of genetic rearrangements in a Type I restriction-modification system (SpnD39III). The rearrangements generate six alternative specificities with distinct methylation patterns, as defined by single-molecule, real-time (SMRT) methylomics. The SpnD39III variants have distinct gene expression profiles. We demonstrate distinct virulence in experimental infection and in vivo selection for switching between SpnD39III variants. SpnD39III is ubiquitous in pneumococci, indicating an essential role in its biology. Future studies must recognize the potential for switching between these heretofore undetectable, differentiated pneumococcal subpopulations in vitro and in vivo. Similar systems exist in other bacterial genera, indicating the potential for broad exploitation of epigenetic gene regulation.
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