ArticlePLoS pathogens2019
DNA methylation from a Type I restriction modification system influences gene expression and virulence in Streptococcus pyogenes.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 64 citations in OpenAlex.
- Acquisition of a novel restriction modification system regulates genetic flux and gene expression in the hypervirulent and globally disseminated CC17 lineage of group B Streptococcus.Nucleic acids research · 2026Article
- Epigenetic regulation in prokaryotes: transcriptional and phenotypic outcomes of DNA methyltransferase activity.FEMS microbiology reviews · 2026Review
- The emerging role of DNA methylation in the pathogenicity of bacterial pathogens.Journal of bacteriology · 2025Review
- Horizontal acquisition of the Type I restriction-modification system enhances bacterial pathogenicity by mediating methylation of transcription factor-encoding genes.Nucleic acids research · 2025Article
- Integrated Analysis of Gene Expression, Protein Synthesis, and Epigenetic Modifications in Alcanivorax borkumensis SK2 Under Iron Limitation.Environmental microbiology reports · 2025Article
- Gene expression analyses on Dickeya solani strains of diverse virulence levels unveil important pathogenicity factors for this species.Scientific reports · 2025Article
- Decoding Adenine DNA Methylation Effects in Streptococcus Mutans: Insights Into Self-DNA Protection and Autoaggregation.Molecular oral microbiology · 2025Article
- Development of a Pre-Modification Strategy to Overcome Restriction-Modification Barriers and Enhance Genetic Engineering inInternational journal of molecular sciences · 2025Article
- The group AInfection and immunity · 2025Article
- Global spread of Streptococcus pyogenes A genomics-supported narrative review.FEMS microbiology reviews · 2025Review
- Epigenetic background of lineage-specific gene expression landscapes of four Staphylococcus aureus hospital isolates.PloS one · 2025Article
- Optimising Transformation Efficiency inInternational journal of molecular sciences · 2024Article
- Efficient and rapid one-step method to generate gene deletions inMicrobiology spectrum · 2024Article
- Changes in DNA methylation contribute to rapid adaptation in bacterial plant pathogen evolution.PLoS biology · 2024Article
- An efficientmBio · 2024Article
- Complete m6A and m4C methylomes for group B streptococcal clinical isolates CJB111, A909, COH1, and NEM316.Microbiology resource announcements · 2024Article
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- Acquisition of Type I methyltransferase via horizontal gene transfer increases the drug resistance ofMicrobial genomics · 2023Article
- Methylome-dependent transformation ofmBio · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
DNA methylation is pervasive across all domains of life. In bacteria, the presence of N6-methyladenosine (m6A) has been detected among diverse species, yet the contribution of m6A to the regulation of gene expression is unclear in many organisms. Here we investigated the impact of DNA methylation on gene expression and virulence within the human pathogen Streptococcus pyogenes, or Group A Streptococcus. Single Molecule Real-Time sequencing and subsequent methylation analysis identified 412 putative m6A sites throughout the 1.8 Mb genome. Deletion of the Restriction, Specificity, and Methylation gene subunits (ΔRSM strain) of a putative Type I restriction modification system lost all detectable m6A at the recognition sites and failed to prevent transformation with foreign-methylated DNA. RNA-sequencing identified 20 genes out of 1,895 predicted coding regions with significantly different gene expression. All of the differentially expressed genes were down regulated in the ΔRSM strain relative to the parent strain. Importantly, we found that the presence of m6A DNA modifications affected expression of Mga, a master transcriptional regulator for multiple virulence genes, surface adhesins, and immune-evasion factors in S. pyogenes. Using a murine subcutaneous infection model, mice infected with the ΔRSM strain exhibited an enhanced host immune response with larger skin lesions and increased levels of pro-inflammatory cytokines compared to mice infected with the parent or complemented mutant strains, suggesting alterations in m6A methylation influence virulence. Further, we found that the ΔRSM strain showed poor survival within human neutrophils and reduced adherence to human epithelial cells. These results demonstrate that, in addition to restriction of foreign DNA, gram-positive bacteria also use restriction modification systems to regulate the expression of gene networks important for virulence.
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