ArticleGut microbes2019
Midbiotics: conjugative plasmids for genetic engineering of natural gut flora.
Article in Gut microbes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- A Biological Approach to Antimicrobial Resistance in New and Old Bacterial Pathogens.Pathogens (Basel, Switzerland) · 2026Review
- Invasive plasmids as ecosystem engineers-from mechanism to application.Essays in biochemistry · 2026Review
- Antibiotic Resistance Crisis: From Bacterial Bioprospecting to Artificial Intelligence.Environmental microbiology reports · 2025Review
- It's complicated: relationships between integrative and conjugative elements and their bacterial hosts.Current opinion in microbiology · 2024Review
- Design, potential and limitations of conjugation-based antibacterial strategies.Microbial biotechnology · 2024Review
- Systematic interrogation of CRISPR antimicrobials in Klebsiella pneumoniae reveals nuclease-, guide- and strain-dependent features influencing antimicrobial activity.Nucleic acids research · 2024Article
- Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.Cancer cell international · 2023Review
- CRISPR-Cas-Based Antimicrobials: Design, Challenges, and Bacterial Mechanisms of Resistance.ACS infectious diseases · 2023Review
- Removal of AMR plasmids using a mobile, broad host-range CRISPR-Cas9 delivery tool.Microbiology (Reading, England) · 2023Article
- Methods of DNA introduction for the engineering of commensal microbes.Engineering microbiology · 2022Review
- Pathogen-Specific Bactericidal Method Mediated by Conjugative Delivery of CRISPR-Cas13a Targeting Bacterial Endogenous Transcripts.Microbiology spectrum · 2022Article
- Plasmid Viability Depends on the Ecological Setting of Hosts within a Multiplasmid Community.Microbiology spectrum · 2022Article
- Superior Conjugative Plasmids Delivered by Bacteria to Diverse Fungi.Biodesign research · 2022Article
- High-efficiency delivery of CRISPR-Cas9 by engineered probiotics enables precise microbiome editing.Molecular systems biology · 2021Article
- CRISPR-based antimicrobials to obstruct antibiotic-resistant and pathogenic bacteria.PLoS pathogens · 2021Review
- CRISPR-Cas, a Revolution in the Treatment and Study of ESKAPE Infections: Pre-Clinical Studies.Antibiotics (Basel, Switzerland) · 2021Review
- Targeted-antibacterial-plasmids (TAPs) combining conjugation and CRISPR/Cas systems achieve strain-specific antibacterial activity.Nucleic acids research · 2021Article
- Indirect Selection against Antibiotic Resistance via Specialized Plasmid-Dependent Bacteriophages.Microorganisms · 2021Article
- Harnessing the CRISPR-Cas Systems to Combat Antimicrobial Resistance.Frontiers in microbiology · 2021Review
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The possibility to modify gut bacterial flora has become an important goal, and various approaches are used to achieve desirable communities. However, the genetic engineering of existing microbes in the gut, which are already compatible with the rest of the community and host immune system, has not received much attention. Here, we discuss and experimentally evaluate the possibility to use modified and mobilizable CRISPR-Cas9-endocing plasmid as a tool to induce changes in bacterial communities. This plasmid system (briefly midbiotic) is delivered from bacterial vector into target bacteria via conjugation. Compared to, for example, bacteriophage-based applications, the benefits of conjugative plasmids include their independence of any particular receptor(s) on host bacteria and their relative immunity to bacterial defense mechanisms (such as restriction-modification systems) due to the synthesis of the complementary strand with host-specific epigenetic modifications. We show that conjugative plasmid in association with a mobilizable antibiotic resistance gene targeting CRISPR-plasmid efficiently causes ESBL-positive transconjugants to lose their resistance, and multiple gene types can be targeted simultaneously by introducing several CRISPR RNA encoding segments into the transferred plasmids. In the rare cases where the midbiotic plasmids failed to resensitize bacteria to antibiotics, the CRISPR spacer(s) and their adjacent repeats or larger regions were found to be lost. Results also revealed potential caveats in the design of conjugative engineering systems as well as workarounds to minimize these risks.
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Registered trials
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.