Novel Approach to the Battle Against Antibiotic Resistance

Antibiotic resistance is a quickly approaching problem facing human health. The misuse of antibiotics has increased the rate at which bacteria develop immunity to our antibiotics, and we are in need of new and effective measures to combat bacterial infections.

One novel idea for tackling the antibiotic resistance epidemic is to use CRISPR technology to target bacteria. The idea was first demonstrated in 2014 at The Rockefeller University and MIT.

Bacteriophages are virus' that specifically target and replicate within bacterial cells

CRISPR is a genetic tool that allows for the precise targeting and editing of specific DNA sequences. It utilizes a Cas protein to cut DNA at specific sites, and guide RNA to direct the Cas protein as to where to cut.

There are several ways of utilizing CRISPR to combat antibiotic resistant bacteria, the most effective method is CRISPR-enhanced phage therapy. CRISPER-enhanced phage therapy works by using engineered bacteriophages that carry CRISPR systems that target specific antibiotic-resistant genes.

The CRISPR payload carried by the bacteriophage will be injected into the bacteria, killing it. The bacteriophage will further replicate itself and spread to more bacteria to repeat the cycle.

This method is most effective because its highly specific and only targets bacteria with the resistance gene. It also replicates itself within the bacteria and spreads itself. The primary challenge to this method is long development process to ensure no unintended side effects.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) was discovered in 1987 by a team of Japanese scientists, led by Yoshizumi Ishino, at Osaka University while studying the iap gene in E. coli.

The different methods that CRISPR can be used to combat antibiotic resistance are all similar due to them all using the same core technology and sharing the same end goal. However, the methods may differ in certain components such as:

• Their delivery mechanisms (carriers vs direct delivery)

• The specific target (entire bacteria vs specific genes)

• Their goal (killing the bacteria vs disabling the bacteria)

Another effective method is to combine CRISPR with traditional antibiotics. The CRISPR-Cas system is administered and once it enters into the bacterial gene, it disables its antibiotic-resistant properties, which then allows us to use traditional antibiotics and eliminate the now weakened bacterial cell. This method extends the efficacy of existing antibiotics but requires precision in its administration to be effective.

It wasn't until 2012 that CRISPR was first used in modern application as a gene editing tool, solidifying itself as the most accessible and versatile system for genetic editing, replacing old systems like ZFNs and TALENs.

It's important that we have different methods due to the need for us to match the bacterial adaptability. Each bacteria demonstrates its own unique properties and the same method of using CRISPR won't be effective across all bacteria. This also allows for different combination methods and iterations for further research.

There are many other methods of using CRISPR in the battle against antibiotic resistance. Targeted gene editing is a precise method of removing bacteria's ability to resist antibiotics, while the bacteria cell keeps intact. Blocking horizontal gene transfer methods stops bacteria from passing on its antibiotic resistance when reproducing. Selective bacterial killing is unspecific on its delivery method and allows the use of nanoparticles as a direct delivery method.

-jasen