ArticleNucleic acids research2018
Excision-reintegration at a pneumococcal phase-variable restriction-modification locus drives within- and between-strain epigenetic differentiation and inhibits gene acquisition.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Type I restriction-modification systems regulate gene expression through DNA topology.Nucleic acids research · 2026Article
- Chromosomal Curing Drives an Arms Race Between Bacterial Transformation and Prophage.Molecular biology and evolution · 2025Article
- Pore-C sequencing identifies episome-driven chromosome conformation perturbations differentiating pneumococcal epigenetic variants.PLoS pathogens · 2025Article
- Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.Nucleic acids research · 2023Article
- Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA.Genome medicine · 2022Article
- The role of interspecies recombination in the evolution of antibiotic-resistant pneumococci.eLife · 2021Article
- Negative frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures.The ISME journal · 2021Article
- Prevalence of phase variable epigenetic invertons among host-associated bacteria.Nucleic acids research · 2020Article
- Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems.PLoS pathogens · 2020Article
- Selective and non-selective bottlenecks as drivers of the evolution of hypermutable bacterial loci.Molecular microbiology · 2020Review
- Phase variation in pneumococcal populations during carriage in the human nasopharynx.Scientific reports · 2020Article
- Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire.Nature reviews. Genetics · 2020Review
- Pathogenic Differences of Type 1 Restriction-Modification Allele Variants in ExperimentalFrontiers in cellular and infection microbiology · 2020Article
- Methylation Warfare: Interaction of Pneumococcal Bacteriophages with Their Host.Journal of bacteriology · 2019Article
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- Recombination of the Phase-VariableJournal of bacteriology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Phase-variation of Type I restriction-modification systems can rapidly alter the sequence motifs they target, diversifying both the epigenetic patterns and endonuclease activity within clonally descended populations. Here, we characterize the Streptococcus pneumoniae SpnIV phase-variable Type I RMS, encoded by the translocating variable restriction (tvr) locus, to identify its target motifs, mechanism and regulation of phase variation, and effects on exchange of sequence through transformation. The specificity-determining hsdS genes were shuffled through a recombinase-mediated excision-reintegration mechanism involving circular intermediate molecules, guided by two types of direct repeat. The rate of rearrangements was limited by an attenuator and toxin-antitoxin system homologs that inhibited recombinase gene transcription. Target motifs for both the SpnIV, and multiple Type II, MTases were identified through methylation-sensitive sequencing of a panel of recombinase-null mutants. This demonstrated the species-wide diversity observed at the tvr locus can likely specify nine different methylation patterns. This will reduce sequence exchange in this diverse species, as the native form of the SpnIV RMS was demonstrated to inhibit the acquisition of genomic islands by transformation. Hence the tvr locus can drive variation in genome methylation both within and between strains, and limits the genomic plasticity of S. pneumoniae.
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