ArticleNucleic acids research2020
4-Methylcytosine DNA modification is critical for global epigenetic regulation and virulence in the human pathogen Leptospira interrogans.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- The Single-Stranded DNA Platform: A Potential Broad-Spectrum Vector for Editing Genes in Prokaryotes: ssDNA May Break Through the Difficulties of Genetic Manipulation on Non-Model Bacteria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Integrative transcriptomic and network analysis reveals small open reading frames associated with cellular adaptive responsees and methylation-linked pathogenicity in Leptospira interrogans.Functional & integrative genomics · 2026Article
- Temperature-dependent dynamics of DNA methylation and plasmid copy number in Yersinia pestis.BMC genomics · 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
- Article
- Evidence for a Putative Regulatory System Consisting of an ECF σInternational journal of molecular sciences · 2025Article
- Identification of virulence genes and clade-specific markers through pan-genomic analysis of Leptospira.BMC microbiology · 2025Article
- Understanding prokaryotic adaptation through advanced DNA methylation detection techniques.The ISME journal · 2025Review
- Epigenetic control of tetrapyrrole biosynthesis by m4C DNA methylation in a cyanobacterium.DNA research : an international journal for rapid publication of reports on genes and genomes · 2024Article
- Intercellular mosaic methylation in fast-growingNAR molecular medicine · 2024Article
- Evolutionary insights into the emergence of virulent Leptospira spirochetes.PLoS pathogens · 2024Article
- Article
- Evolutionary insights into the emergence of virulentbioRxiv : the preprint server for biology · 2024Article
- Autoimmune disease: a view of epigenetics and therapeutic targeting.Frontiers in immunology · 2024Review
- PacBio sequencing of human fecal samples uncovers the DNA methylation landscape of 22 673 gut phages.Nucleic acids research · 2023Article
- Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.Microbiology spectrum · 2023Article
- Extension of bacterial rDNA sequencing for simultaneous methylation detection and its application in microflora analysis.Scientific reports · 2023Article
- Transcription start site mapping and small RNA profiling of Leptospira biflexa serovar Patoc.World journal of microbiology & biotechnology · 2023Article
- Growth condition-dependent differences in methylation imply transiently differentiated DNA methylation states in Escherichia coli.G3 (Bethesda, Md.) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In bacteria, DNA methylation can be facilitated by 'orphan' DNA methyltransferases lacking cognate restriction endonucleases, but whether and how these enzymes control key cellular processes are poorly understood. The effects of a specific modification, 4-methylcytosine (4mC), are even less clear, as this epigenetic marker is unique to bacteria and archaea, whereas the bulk of epigenetic research is currently performed on eukaryotes. Here, we characterize a 4mC methyltransferase from the understudied pathogen Leptospira spp. Inactivating this enzyme resulted in complete abrogation of CTAG motif methylation, leading to genome-wide dysregulation of gene expression. Mutants exhibited growth defects, decreased adhesion to host cells, higher susceptibility to LPS-targeting antibiotics, and, importantly, were no longer virulent in an acute infection model. Further investigation resulted in the discovery of at least one gene, that of an ECF sigma factor, whose transcription was altered in the methylase mutant and, subsequently, by mutation of the CTAG motifs in the promoter of the gene. The genes that comprise the regulon of this sigma factor were, accordingly, dysregulated in the methylase mutant and in a strain overexpressing the sigma factor. Our results highlight the importance of 4mC in Leptospira physiology, and suggest the same of other understudied species.
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