ArticleProceedings of the National Academy of Sciences of the United States of America2011
Conjugative DNA transfer into human cells by the VirB/VirD4 type IV secretion system of the bacterial pathogen Bartonella henselae.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
- Type IV secretion systems: reconciling diversity through a unified nomenclature.FEMS microbiology reviews · 2026Review
- ThemicroLife · 2025Review
- Pipolins are bimodular platforms that maintain a reservoir of defense systems exchangeable with various bacterial genetic mobile elements.Nucleic acids research · 2024Article
- Delivery of functional Cas:DNA nucleoprotein complexes into recipient bacteria through a type IV secretion system.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology.MedComm · 2023Review
- DNA Transport through the Dynamic Type IV Secretion System.Infection and immunity · 2023Review
- Recruitment of heterologous substrates by bacterial secretion systems for transkingdom translocation.Frontiers in cellular and infection microbiology · 2023Review
- Genetic modification, intercellular communication, and epigenetic regulation in plants: An outlook.Biochemical and biophysical research communications · 2022Review
- Novel directions of precision oncology: circulating microbial DNA emerging in cancer-microbiome areas.Precision clinical medicine · 2022Review
- Structural basis for effector recognition by an antibacterial type IV secretion system.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Trans-Kingdom Conjugation within Solid Media fromInternational journal of molecular sciences · 2019Article
- Expression of a novel class of bacterial Ig-like proteins is required for IncHI plasmid conjugation.PLoS genetics · 2019Article
- Pathways of DNA Transfer to Plants fromAnnual review of phytopathology · 2019Article
- Antimicrobial activity and carbohydrate metabolism in the bacterial metagenome of the soil-living invertebrate Folsomia candida.Scientific reports · 2019Article
- Inhibiting bacterial secretion systems in the fight against antibiotic resistance.MedChemComm · 2019Review
- Type IV secretion in Gram-negative and Gram-positive bacteria.Molecular microbiology · 2018Review
- Rationale redesign of type III secretion systems: toward the development of non-pathogenic E. coli for in vivo delivery of therapeutic payloads.Current opinion in microbiology · 2018Review
- Substrate translocation involves specific lysine residues of the central channel of the conjugative coupling protein TrwB.Molecular genetics and genomics : MGG · 2017Article
- Human Infection with Burkholderia thailandensis, China, 2013.Emerging infectious diseases · 2017Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial type IV secretion systems (T4SS) mediate interbacterial conjugative DNA transfer and transkingdom protein transfer into eukaryotic host cells in bacterial pathogenesis. The sole bacterium known to naturally transfer DNA into eukaryotic host cells via a T4SS is the plant pathogen Agrobacterium tumefaciens. Here we demonstrate T4SS-mediated DNA transfer from a human bacterial pathogen into human cells. We show that the zoonotic pathogen Bartonella henselae can transfer a cryptic plasmid occurring in the bartonellae into the human endothelial cell line EA.hy926 via its T4SS VirB/VirD4. DNA transfer into EA.hy926 cells was demonstrated by using a reporter derivative of this Bartonella-specific mobilizable plasmid generated by insertion of a eukaryotic egfp-expression cassette. Fusion of the C-terminal secretion signal of the endogenous VirB/VirD4 protein substrate BepD with the plasmid-encoded DNA-transport protein Mob resulted in a 100-fold increased DNA transfer rate. Expression of the delivered egfp gene in EA.hy926 cells required cell division, suggesting that nuclear envelope breakdown may facilitate passive entry of the transferred ssDNA into the nucleus as prerequisite for complementary strand synthesis and transcription of the egfp gene. Addition of an eukaryotic neomycin phosphotransferase expression cassette to the reporter plasmid facilitated selection of stable transgenic EA.hy926 cell lines that display chromosomal integration of the transferred plasmid DNA. Our data suggest that T4SS-dependent DNA transfer into host cells may occur naturally during human infection with Bartonella and that these chronically infecting pathogens have potential for the engineering of in vivo gene-delivery vectors with applications in DNA vaccination and therapeutic gene therapy.
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