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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing
Michelle M C Buckner1, Maria Laura Ciusa1, Laura J V Piddock1
1Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham B15 2TT, UK.
Abstract:
Antimicrobial resistance (AMR) is a global problem hindering treatment of bacterial infections, rendering many aspects of modern medicine less effective. AMR genes (ARGs) are frequently located on plasmids, which are self-replicating elements of DNA. They are often transmissible between bacteria, and some have spread globally. Novel strategies to combat AMR are needed, and plasmid curing and anti-plasmid approaches could reduce ARG prevalence, and sensitise bacteria to antibiotics. We discuss the use of curing agents as laboratory tools including chemicals (e.g. detergents and intercalating agents), drugs used in medicine including ascorbic acid, psychotropic drugs (e.g. chlorpromazine), antibiotics (e.g. aminocoumarins, quinolones and rifampicin) and plant-derived compounds. Novel strategies are examined; these include conjugation inhibitors (e.g. TraE inhibitors, linoleic, oleic, 2-hexadecynoic and tanzawaic acids), systems designed around plasmid incompatibility, phages and CRISPR/Cas-based approaches. Currently, there is a general lack of in vivo curing options. This review highlights this important shortfall, which if filled could provide a promising mechanism to reduce ARG prevalence in humans and animals. Plasmid curing mechanisms which are not suitable for in vivo use could still prove important for reducing the global burden of AMR, as high levels of ARGs exist in the environment.
Insights
Novel strategies targeting plasmids, which carry antimicrobial resistance genes (ARGs), are crucial for combating bacterial infections. Developing in vivo plasmid curing methods could significantly reduce ARG prevalence in humans and animals.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Antimicrobial resistance (AMR) is a significant global health threat, compromising modern medicine.
- Antimicrobial resistance genes (ARGs) are often located on transmissible plasmids, facilitating their spread.
- Effective strategies are needed to reduce ARG prevalence and restore antibiotic efficacy.
Purpose of the Study:
- To review current and novel strategies for combating antimicrobial resistance through plasmid targeting.
- To highlight the potential of plasmid curing and anti-plasmid approaches.
- To identify the critical need for in vivo plasmid curing methods.
Main Methods:
- Discussion of various plasmid curing agents used in laboratory settings (chemicals, drugs, plant compounds).
- Examination of novel anti-plasmid strategies including conjugation inhibitors, plasmid incompatibility systems, phages, and CRISPR/Cas approaches.
- Review of existing literature on plasmid curing and anti-plasmid technologies.
Main Results:
- A wide range of laboratory-based plasmid curing agents have been identified.
- Emerging strategies like conjugation inhibitors and CRISPR/Cas offer new avenues for anti-plasmid interventions.
- There is a significant lack of effective in vivo plasmid curing options.
Conclusions:
- Plasmid curing and anti-plasmid strategies hold promise for reducing ARG prevalence and sensitizing bacteria to antibiotics.
- Filling the gap in in vivo curing methods could provide a powerful tool against AMR in clinical and veterinary settings.
- Even ex vivo plasmid curing methods can contribute to reducing the environmental burden of ARGs.
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