Antimicrobial resistance (AMR) is a major global threat, nearly 5 million deaths annually are reported due to bacterial resistance to antibiotics which fails to treat infections.
It is also predicted that AMR would kill more people annually than cancer by the year 2050.[1].
The study conducted by the University of Exeter used the CRISPR-Cas9 Gene editing system to reduce resistant gene-carrying plasmids by several means.
How Do Bacteria Gain Resistance to Antibiotics?
Bacteria transfer antibiotic-resistant genes to each other through plasmids: a small circular DNA molecule found in bacteria, they can also replicate fast.
A bacterium can become resistant to multiple antibiotics at once by picking up a single plasmid, through this they become multidrug-resistant.
The transfer can occur in multiple mediums, for instance, in our bodies and also in environmental systems.
Removing AMR Plasmids using CRISPR-Cas9 Gene Editing
CRISPR-Cas9 functions by cutting the DNA at two sites, leaving two blunt ends.
Using this, earlier, CRISPR-Cas-technology was used to remove plasmids encoding AMR genes from target bacteria, through plasmid acting as a vector for the transport of cas9.
For the feasibility of removing AMR-containing plasmids from multiple microbial groups this technology, an efficient, universal host vector is needed.
Hence, the broad host range plasmid pKJK5 encodes cas9 programmed to target an AMR gene.
The engineered plasmid pKJK5, specifically engineered to target the resistance gene for the antibiotic-gentamicin has the ability to block the uptake of AMR plasmids and to remove resident plasmids from Escherichia coli, a Gram-negative bacteria.
pKJK5 blocked the uptake of AMR plasmid in the coliform bacterium, which is associated with pigs and humans, and also in two species of Pseudomonas, a bacterium commonly found in the environment. [2]
One of the authors of the study, David Walker-Sünderhauf, of the University of Exeter, stressed the threat level of AMR bacterium, by stating, “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.”
References
- Fergus Walsh, ‘Superbugs to kill ‘more than cancer’ by 2050’, BBC, 11 December 2014, “Drug resistant infections will kill an extra 10 million people a year worldwide – more than currently die from cancer – by 2050 unless action is taken, a study says.”, https://www.bbc.com/news/health-30416844[↩]
- David Walker-Sünderhauf, ‘Removal of AMR plasmids using a mobile, broad host-range CRISPR-Cas9 delivery tool’, Microbiology Society, 25 May 2023, “Antimicrobial resistance (AMR) genes are widely disseminated on plasmids. Therefore, interventions aimed at blocking plasmid uptake and transfer may curb the spread of AMR.”, https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.001334[↩]
