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Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Indirect Selection against Antibiotic Resistance via Specialized Plasmid-Dependent Bacteriophages
Reetta Penttinen1,2, Cindy Given1, Matti Jalasvuori1
1Department of Biological and Environmental Science and Nanoscience Center, University of Jyväskylä, Survontie 9C, P.O.Box 35, FI-40014 Jyväskylä, Finland.
Abstract:
Antibiotic resistance genes of important Gram-negative bacterial pathogens are residing in mobile genetic elements such as conjugative plasmids. These elements rapidly disperse between cells when antibiotics are present and hence our continuous use of antimicrobials selects for elements that often harbor multiple resistance genes. Plasmid-dependent (or male-specific or, in some cases, pilus-dependent) bacteriophages are bacterial viruses that infect specifically bacteria that carry certain plasmids. The introduction of these specialized phages into a plasmid-abundant bacterial community has many beneficial effects from an anthropocentric viewpoint: the majority of the plasmids are lost while the remaining plasmids acquire mutations that make them untransferable between pathogens. Recently, bacteriophage-based therapies have become a more acceptable choice to treat multi-resistant bacterial infections. Accordingly, there is a possibility to utilize these specialized phages, which are not dependent on any particular pathogenic species or strain but rather on the resistance-providing elements, in order to improve or enlengthen the lifespan of conventional antibiotic approaches. Here, we take a snapshot of the current knowledge of plasmid-dependent bacteriophages.
Insights
Plasmid-dependent bacteriophages can combat antibiotic resistance by eliminating plasmids from bacteria. These specialized viruses offer a novel strategy to enhance current antibiotic treatments against multi-drug resistant pathogens.
Area of Science:
- Microbiology
- Genetics
- Virology
Background:
- Antibiotic resistance genes in Gram-negative pathogens are often located on mobile genetic elements like conjugative plasmids.
- Continuous antimicrobial use selects for plasmids carrying multiple resistance genes, accelerating resistance.
- Plasmid-dependent bacteriophages specifically infect bacteria harboring certain plasmids.
Purpose of the Study:
- To review the current knowledge on plasmid-dependent bacteriophages.
- To explore their potential in combating antibiotic resistance.
- To assess their role in enhancing conventional antibiotic therapies.
Main Methods:
- Review of existing scientific literature on plasmid-dependent bacteriophages.
- Analysis of their mechanisms of action against plasmids.
- Evaluation of their therapeutic potential in combating antimicrobial resistance.
Main Results:
- Plasmid-dependent phages can reduce plasmid load in bacterial communities.
- They can induce mutations rendering remaining plasmids untransferable.
- This leads to the loss of multiple antibiotic resistance genes.
- Phage therapy is emerging as a viable option for multi-resistant infections.
Conclusions:
- Plasmid-dependent bacteriophages represent a promising tool to combat antibiotic resistance.
- They can be utilized to disarm antibiotic resistance elements, not specific strains.
- This approach could extend the efficacy of existing antibiotic treatments.
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