University of Exeter researchers have used the CRISPR-Cas gene editing system to create a plasmid that targets antibiotic resistance genes, effectively preventing and reversing resistance. The tool shows promising early results in laboratory experiments, opening up a potential new way to combat the global health threat of antimicrobial resistance.
A new tool that could help reduce the spread of antimicrobial resistance is showing early promise, through exploiting a bacterial immune system as a gene editing tool.
Antimicrobial resistance is a major global threat, with nearly five million deaths annually resulting from antibiotics failing to treat infection, according to the World Health Organisation.
Bacteria often develop resistance when resistant genes are transported between hosts. One way that this occurs is via plasmids – circular strands of DNA, which can spread easily between bacteria, and swiftly replicate. This can occur in our bodies, and in environmental settings, such as waterways.
The University of Exeter team harnessed the CRISPR-Cas gene editing system, which can target specific sequences of DNA, and cuts through them when they are encountered. The researchers engineered a plasmid that can specifically target the resistance gene for Gentamicin – a commonly used antibiotic.
A promising new gene editing tool that could be key to reducing the spread of Antimicrobial Resistance (AMR) has been developed by researchers at the University of Exeter University, UK. Credit: Microbiology Society
In laboratory experiments, the new research, published today (May 25) in the journal Microbiology, found that the plasmid protected its host cell from developing resistance. Furthermore, researchers found that the plasmid effectively targeted antimicrobial resistant genes in hosts to which it transferred, reversing their resistance.
Lead author David Walker-Sünderhauf, of the University of Exeter, said: “Antimicrobial resistance threatens to outstrip covid in terms of the number of global deaths. We urgently need new ways to stop resistance spreading between hosts. Our technology is showing early promise to eliminate resistance in a wide range of different bacteria. Our next step is to conduct experiments in more complex microbial communities. We hope one day it could be a way to reduce the spread of antimicrobial resistance in environments such as sewage treatment plants, which we know are breeding grounds for resistance.”
Reference: “Removal of AMR plasmids using a mobile, broad host-range, CRISPR-Cas9 delivery tool” by David Walker-Sünderhauf, Uli Klümper, Elizabeth Pursey, Edze R. Westra, William H. Gaze and Stineke van Houte, 25 May 2023, Microbiology.
The research is supported by GW4, the Medical Research Council, the Lister Institute, and JPI-AMR.
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