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Editing Out the Enemy: Using CRISPR-Cas9 Genetic
Engineering Machinery to Fight CR-hvKP Superbugs
By Chloe Howard
Introduction
Imagine a future where a simple infection could become deadly because antibiotics
no longer work. This is not science fiction. It’s already happening due to
antibiotic-resistant bacteria like Carbapenem-Resistant Hypervirulent Klebsiella
pneumoniae (CR-hvKP), one of the World Health Organisation's top priority
superbugs. Genetic engineering, especially the CRISPR-Cas9 technique, offers a
revolutionary tool to fight back by editing bacterial DNA and eradicating both
resistance and virulence genes.
What Is Genetic Engineering and CRISPR?
Genetic engineering is the direct modification of an organism’s DNA using
biotechnology. CRISPR-Cas9, discovered in 2012, is a gene-editing tool that works
like molecular scissors. It can identify a specific DNA sequence and cut it, allowing
scientists to delete or replace faulty genes.
Why CR-hvKP Is a Problem
Klebsiella pneumoniae is a bacterium commonly
found in the human gut, but certain strains have
developed resistance to powerful carbapenem
antibiotics. These resistant strains, CR-hvKP, are
extremely dangerous because they combine
resistance with high virulence, meaning they can
cause severe infections even in healthy people.
Outbreaks of CR-hvKP have a 21.95% higher fatality
rate than E. coli. To be so powerful, these bacteria
carry multiple resistance genes like blaNDM and
blaKPC, and virulence genes like rmpA and iucA that
allow rapid spread. This is shown in fig 1.
How Genetic Engineering Can Help
One promising solution involves using engineered
bacteriophages (viruses that infect bacteria) to deliver
CRISPR-Cas systems into CR-hvKP cells. Once inside, the CRISPR-Cas9 enzyme
can be guided to target both resistance genes and virulence genes, cutting them
and disabling their function. This can restore sensitivity to antibiotics and reduce the
bacteria's ability to cause disease. In 2019, researchers successfully used CRISPR
to disrupt resistance genes in E. coli. A similar strategy could work for CR-hvKP.
In class, we explored how restriction enzymes cut
DNA at specific sequences and how gel
electrophoresis can separate those fragments by
size. These techniques helped us understand how
scientists locate and analyze genes of interest before
editing them. In real-world applications,
CRISPR-Cas9 uses a similar principle of precise
cutting, but instead of random enzymes, it uses a
guide RNA to direct the Cas9 protein to an exact
DNA sequence. This process is shown in fig 2. Our
“Clone That Gene” activity further showed how
plasmids can carry antibiotic resistance and virulence
genes, just like those found in CR-hvKP. CRISPR can
be programmed to disable these genes, reducing the
bacteria’s ability to cause disease. By simulating how
a gene could be inserted into or removed from a
plasmid, we gained insight into how biotechnology tools like CRISPR build on our
lab techniques to engineer real genetic solutions to urgent medical challenges.
Benefits and Considerations
The main benefit of CRISPR-based treatments is that they could be more precise
and effective than traditional antibiotics, targeting only harmful bacteria and leaving
beneficial microbiota unharmed. However, there are concerns about off-target
effects, ethical issues, and the possibility of edited genes escaping into the
environment. These unintended edits could potentially disrupt other genes, leading
to unforeseen consequences in microbial communities or human health.
Conclusion
With CR-hvKP and other superbugs on the rise, genetic engineering offers a
powerful new strategy for tackling these threats. While not without risks,
CRISPR-based solutions could lead to effective treatments that go beyond
conventional antibiotics. By understanding the science in the classroom and
applying it to real-world problems, we are one step closer to being the generation
that edits out our microbial enemies.
References
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