Genetically Resistant Superbugs

What are superbugs?

Superbugs are a form of bacteria that have evolved resistance to modern day drugs and antibiotics. Tools that were previously used to combat bacterial diseases become ineffective against these organisms. Many different types of bacteria can be classified as superbugs. Superbugs are a threat to public health because they infect at least 2 million people and kill 23,000 annually (Antibiotic, 2018).

How is a superbug formed?

Antibiotics and drugs are used to kill off harmful bacteria. However, these tools cannot always kill 100% of their targets. Some bacteria are immune. Superbugs are formed when bacteria that are immune survive and reproduce, increasing the number of bacteria that are genetically resistant. This phenomena is often caused by the overuse or misuse of these antibiotics and drugs. For example, the first antibiotic discovered, penicillin, was widely celebrated because it could control bacterial infections of soldiers in WWII. Just ten years after the introduction of this celebrated solution penicillin was no longer effective against much of the bacteria it was before. Penicillin works by targeting proteins in bacteria, preventing it from forming a new cell wall upon division (Britannica, 2018). This inhibited the bacteria's ability to reproduce. However, in a population of bacteria, there may be a few that have a mutation that makes them immune to this antibiotic. The bacteria that are immune are left alive after the use of the antibiotic. These resistant bacterium continue to divide, and soon they form a new, resistant population. Superbugs are bacteria that are resistant to multiple different drugs and antibiotics.

CRISPR-Cas9 Solution

What is CRISPR-Cas9?

CRISPR and Cas9 is a combination of DNA sequences and enzymes work together to edit specific sections of genes. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which means a specialized pattern of nucleotides that repeats throughout a strand of DNA with unique sections in between (spacers). CRISPR is paired with an associated enzyme called Cas (CRISPR associated proteins). CRISPR can be found naturally occurring in bacterium. It is often used as a defense mechanism against attacking organisms.

How does it work?

CRISPR acts like a pair of scissors that cuts a targeted section of DNA in order to remove a desired trait. Another section of DNA can also be used to replace the removed section.
In bacterium, different sections of DNA from the organism match the DNA in attacking viruses and is used as an identifier. This DNA sequence is paired with a Cas enzyme that can then identify the DNA sequence in attacking organisms and remove it, rendering them ineffective.

There are a few different steps CRISPR follows to actually edit the DNA:

  1. gRNA, or guide RNA is used to identify the target DNA sequence that is going to be cleaved, or cut out.
  2. the Cas9 protein surrounds the target section of DNA it wants to edit.
  3. the DNA strand divides in a bubble by separating the nucleotides and the gRNA attaches to the target section.
  4. Cas9 "cuts" the DNA in the desired spot based on the gRNA and removes the target section.
  5. If necessary, the removed section of DNA can be replaced or repaired to create desired change.

CRISPR in the Classroom by Simon Levien

How can it be used to combat superbugs?

CRISPR gene editing has many possible applications from adding desired traits to food or removing certain traits from humans. It can also be used as a means to combat superbugs that are resistant to other techniques. Scientists can select desired genes for bacteria to target and cut for patients in the same way bacteria do naturally. This will allow them to accurately and effectively kill the bacteria they are targeting and eliminating the disease. This is also a more precise genome editing tool than many other techniques used today like homologous recombination, zinc fingers, and TALENs.

References

Antibiotic / Antimicrobial Resistance (AR / AMR): Biggest Threats and Data. (2018, September 10). Retrieved from https://www.cdc.gov/drugresistance/biggest_threats.html

Antimicrobial (Drug) Resistance. (2018, November 13). Retrieved from https://www.niaid.nih.gov/research/antimicrobial-resistance

Britannica, T. E. (2018, October 31). Penicillin. Retrieved from https://www.britannica.com/science/penicillin

Levien, S. (2017, July 29). CRISPR in the Classroom by Simon Levien. Retrieved from http://www.njsta.org/news/crispr-in-the-classroom-by-simon-levien

Ventola, L. C. (2015). The Antibiotic Resistance Crisis. P T, 40(4). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/