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A new tool that could help slow the spread of antimicrobial resistance is showing promise by exploiting a bacterial immune system as a gene-editing tool.
Antimicrobial resistance is a major global threat, with nearly five million deaths annually as a result of antibiotics failing to treat the infection, according to the World Health Organization.
Bacteria often develop resistance when resistance genes are carried between hosts. One way this occurs is through plasmids, circular strands of DNA, which can easily spread between bacteria and replicate rapidly. This can occur in our bodies and in environmental settings, such as waterways.
The Exeter team took advantage of the CRISPR-Cas gene-editing system, which can target specific DNA sequences and cuts them out when found. The researchers designed a plasmid that can specifically target the gene for resistance to gentamicin, a commonly used antibiotic.
In laboratory experiments, the new research, published in Microbiology, discovered that the plasmid protected its host cell from developing resistance. In addition, the researchers found that the plasmid effectively targeted antimicrobial-resistant genes in the hosts it was transferred to, reversing their resistance.
Lead author David Walker-Sünderhauf, from the University of Exeter, said: “Antimicrobial resistance threatens to overtake covid in terms of the number of global deaths. We urgently need new ways to stop the spread of resistance among hosts. Our technology is showing early promise for eliminating resistance in a wide range of different bacteria. Our next step is to conduct experiments in more complex microbial communities. We hope that one day it may be a way to reduce the spread of resistance to hosts. antimicrobials in settings like sewage treatment plants, which we know are breeding grounds for resistance.”
The research is supported by GW4, the Medical Research Council, the Lister Institute, and JPI-AMR. The paper is titled “AMR Plasmid Deletion Using a Wide-Host Range Mobile CRISPR-Cas9 Delivery Tool” and is published at Microbiology.
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