ArticleProceedings of the National Academy of Sciences of the United States of America2019
Systematic evasion of the restriction-modification barrier in bacteria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- A user-friendly strategy to engineer tailored intermediate strains for overcoming combined type I and type II restriction-modification barriers inSynthetic and systems biotechnology · 2027Article
- The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome.eLife · 2026Article
- Genome-Wide DNA Methylation and Restriction-Modification Systems inMicroorganisms · 2026Article
- Evading native restriction-modification systems improves electroporation efficiency of the methanotrophApplied and environmental microbiology · 2026Article
- 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
- Genetic engineering ofMicrobial genomics · 2026Article
- A syntenic pangenome of Gardnerella reveals novel plasmids and phage, taxonomic boundaries, and species-level stratification of metabolic and virulence potential.Nature communications · 2026Article
- Synthetically designed anti-defense proteins overcome barriers to bacterial transformation and phage infection.Nature communications · 2026Article
- Genetic modification of intractable bacterial clones by heat shock-facilitated phage transduction.Cell reports methods · 2026Article
- The genetic landscape of antibiotic sensitivity inScience advances · 2026Article
- Methods for the Evasion of Restriction-Modification Systems During Genetic Engineering of Fusobacterium Species.Methods in molecular biology (Clifton, N.J.) · 2026Article
- An ISFrontiers in microbiology · 2026Article
- Removal and bypass of restriction modification systems increases transformation efficiency ofFrontiers in microbiology · 2026Article
- Targeted Deletion of the Cytopathogenic Toxin A Gene in Sneathia vaginalis.Molecular microbiology · 2025Article
- UsingACS synthetic biology · 2025Article
- Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases.Science (New York, N.Y.) · 2025Article
- Comparative and functional genomic analysis of foreign DNA defense mechanisms inMicrobiology spectrum · 2025Article
- Comparative Genomic Assessment of the Cupriavidus necator Species for One-Carbon Based Biomanufacturing.Microbial biotechnology · 2025Article
- Advances in Diversity, Evolutionary Dynamics and Biotechnological Potential of Restriction-Modification Systems.Microorganisms · 2025Review
- Highly efficient CRISPR-Cas9 base editing inApplied and environmental microbiology · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Bacteria that are recalcitrant to genetic manipulation using modern in vitro techniques are termed genetically intractable. Genetic intractability is a fundamental barrier to progress that hinders basic, synthetic, and translational microbiology research and development beyond a few model organisms. The most common underlying causes of genetic intractability are restriction-modification (RM) systems, ubiquitous defense mechanisms against xenogeneic DNA that hinder the use of genetic approaches in the vast majority of bacteria and exhibit strain-level variation. Here, we describe a systematic approach to overcome RM systems. Our approach was inspired by a simple hypothesis: if a synthetic piece of DNA lacks the highly specific target recognition motifs for a host's RM systems, then it is invisible to these systems and will not be degraded during artificial transformation. Accordingly, in this process, we determine the genome and methylome of an individual bacterial strain and use this information to define the bacterium's RM target motifs. We then synonymously eliminate RM targets from the nucleotide sequence of a genetic tool in silico, synthesize an RM-silent "SyngenicDNA" tool, and propagate the tool as minicircle plasmids, termed SyMPL (SyngenicDNA Minicircle Plasmid) tools, before transformation. In a proof-of-principle of our approach, we demonstrate a profound improvement (five orders of magnitude) in the transformation of a clinically relevant USA300 strain of
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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.