Gene editing tools have the potential to contribute significantly to the reduction of antimicrobial resistance (AMR). AMR is a global health concern where microorganisms, such as bacteria, viruses, and parasites, develop resistance to the drugs used to treat them, rendering these drugs ineffective.
A new tool which 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.
“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.”
David Walker-Sünderhauf
The 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 which can specifically target the resistance gene for Gentamicin – a commonly used antibiotic.
In laboratory experiments, the new research, published in 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.
Gene editing tools can aid in understanding the underlying genetic mechanisms that confer resistance in bacteria. By studying the genetic components involved, researchers can develop strategies to overcome or prevent resistance.
CRISPR-Cas9 is one of the most well-known and widely used gene editing tools. It allows scientists to precisely modify genetic material, including the genes of microorganisms. By targeting the specific genes responsible for antibiotic resistance in bacteria, researchers can potentially disrupt or disable those genes, making the bacteria susceptible to antibiotics once again.
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.”
Gene editing can facilitate the development of novel antimicrobial agents that target resistant bacteria. By modifying the genetic material of these microorganisms, researchers can potentially weaken their defenses and increase the effectiveness of existing antibiotics or create new therapeutic options.
