CRISPR-Cas could hold the solution to AMR
07 March 2019
New research carried out at the University of Exeter has found a novel way to tackle the growing issue of antimicrobial resistance (AMR) using the gene editing technology CRISPR-Cas.
Many of the genes that code for AMR are found on accessory genetic elements such as plasmids. Plasmids are rings of DNA that can spread easily between bacteria and replicate. Plasmids are not part of the bacteria’s DNA, but can distribute traits like AMR between cells.
Researchers have engineered a plasmid to specifically target the resistance gene for Gentamicin, a broad-spectrum antibiotic used for a wide range of bacterial infections. When the plasmid identifies the gene for Gentamicin, it cuts out the DNA, removing the resistance and making the cell susceptible to the antibiotic.
When using this new technique, the researchers found that they could lower resistance levels by 33% compared with a control treatment using a plasmid engineered in the same way, but without specifically targeting the Gentamicin-resistance gene.
The researchers are able to cut out the genes for resistance by using CRISPR-Cas; a gene editing technology that allows for DNA to be altered by cutting it in a desired location. It is based on the antiviral CRISPR-Cas (Cas9) defence system that bacteria use against viruses. Scientists engineer a synthetic Cas9 enzyme and pair it with guide RNA which tells the Cas9 where to cut the DNA, allowing genes to be removed and if desired, replaced with new genes.
David Sünderhauf, researcher at the University of Exeter said, “We’re facing a huge challenge with AMR in the coming years, and it is important to investigate different approaches to solve this problem.”
AMR develops when pathogenic bacteria evolve resistance to an antibiotic - as these bacteria have a significant evolutionary advantage over others in their species, they survive, reproduce, and the genes for AMR spread. Over-use of antibiotics in the farming industry, not using antibiotics correctly, such as using them for viral infections or not finishing the course of antibiotics, allows resistance to spread even faster.
Exacerbating the issue further is bacteria’s ability to transfer genes horizontally, where genetic material is passed between individuals without the need to reproduce. This process is done with plasmids, and can occur between species, leading to the development of AMR in a wide range of bacteria.
While still in the early stages of research, this new approach to tackling AMR has huge potential, David Sünderhauf said; “Once fully developed we could use this approach to keep our current antibiotics working by removing resistance genes from clinical pathogens or from the environment.”
David Sünderhauf will present his findings at the 2019 Microbiology Society Annual Conference. His poster, ‘AMR gene removal by conjugative delivery of CRISPR-Cas9’, will be available to view from Wednesday 10 April to Thursday 11 April in Hall 1D.Image: mcmurryjulie/Pixabay.
