Biotechnology Genetics

CRISPR May Be Key in Fight Against Antibiotic Resistant!

CRISPR antibiotics resistant

Scientists developed a novel approach to killing bacteria using CRISPR gene editing technology, thus, bypassing the need for antibiotics.

What is Antibiotics Resistance?

Antibiotics are those drugs or medications that can kill certain kinds of microorganisms. Most antibiotics work by disrupting the natural biological process of bacteria including cell division and thriving abilities. Over time, those microorganisms often develop resistance to the antibiotics, so-called antibiotic resistance. When this happens, antibiotics that previously would have killed the bacteria, or stopped them from multiplying, no longer work.

How Antibiotics Resistance Occur?

There are several reasons for this;

Most of the time patients do not use antibiotics for their specific duration. For example, if a doctor advises you to use antibiotics for one month, then use it for one month. However, unfortunately, most of the people will stop it, the moment they feel better after a week or two. As a result, some of the bacteria are not killed, and via chemical signaling and other methods, learn about the antibiotics, its mode of action and become resistant to it.

Video: the most chilling demonstration of antibacterial resistance in action!

Moreover, sometimes patients use antibiotics without consulting doctors and even for diseases that are not bacterial. The most common being cold and flu, which is caused by viral agents, using antibiotics for them is entirely useless. This misuse makes the bacteria resistant to them and leads to antibiotic resistance.

Misuse and overuse of antibiotics mean they are losing their power. And the more they are used, the more chance bacteria have to become resistant to them.

So, it’s always better to consulate professional doctor before using antibiotics.

Currently, antibiotic resistance is a growing epidemic and could result in 10 million deaths each year by 2050 if not resolved. Moreover, each year 23,000 Americans only die as a result of antibiotics resistance microbes including Klebsiella pneumonia, and Methicillin-resistant Staphylococcus aureus (MRSA). Other involves Clostridium difficile, Extensively Drug-Resistant Mycobacterium Tuberculosis (XDR-TB), Neisseria gonorrhoeae, Shiga toxin-producing Escherichia coli and more. On most of them, current antibiotics are ineffective.

 

Antibiotics resistance crispr
Projections of deaths from drug-resistant infections by 2050

Currently, the search for new antibiotics is the most important goals of our time. However, unfortunately, bacteria again become resistant against most of them.

Now, scientists are thinking outside the box and looking for alternative approaches to tackle the antibiotic-resistance problem.

What is CRISPR Gene Editing?

The hottest scientific breakthrough, so-called CRISPR is a powerful gene editing tool that has the potential to modify the genome of almost any organism.

It basically evolved as a bacterial immune system where it cut and later store foreign particle (usually viruses). Scientist hijacked this cut and paste property of CRISPR and then used as a gene-editing tool.

CRISPR could be used to target those genes that are responsible for causing antibiotics resistance.

Explore more about CRISPR: What is CRISPR Cas9?

CRISPR Antibiotics

Recently, a study published in Nature Microbiology, entitled “Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi”, where researchers used a variant of CRISPR called CRISPR interference (CRISPRi). The technique involves the CRISPR does not cut the DNA, but rather recognize a target sequence and sit there. They are thereby blocking the access of proteins to that specific DNA sequence. As a result, the products from that particular DNA decreases.

In this study, researchers showed that by making CRISPRi mobile, i.e. modifying it in such a way to be easily transferred into target DNA. CRISPRi from the lab-grown E.coli was transferred into various pathogenic bacterial strains like pseudomonas, listeria, staphylococcus via bacterial conjugation. Once inserted, the sgRNA from CRISPRi interacted with those genes which are thought to interfere with the activity of antibiotics.

The dCas9 (deactivated Cas9) blocked these specific genes. The strains became sensitive to the antibiotics, even when antibiotics were used in low amount.

In this way, scientists can program CRISPRi to overcome the global problem of antibiotic resistivity.

Research by School of Chemistry, Manchester University

Moreover, researchers from the Manchester University, school of chemistry, reported that by using CRISPR/cas9 they have successfully discovered a novel biological pathway for the production of antibiotics called Malonomycin. These novel antibiotics will be able to fight off resistant bacterial strains much better than already present antibiotics.

“The rapid rise of antibiotic-resistant pathogens is one of the foremost global health concerns of modern times. Now, using a combination of bioinformatics, [CRISPR/Cas9] gene editing, and in vitro experiments, we have discovered a highly unusual biosynthetic pathway to the antibiotics Malonomycin. This could pave the way for a new kind of antibiotic production process,” said Jason Micklefield, leader of the study, and professor of Chemical Biology at the Manchester Institute of Biotechnology.

Research by the University of Colorado

In 2018, a team of researchers from the University of Colorado developed a technique called Controlled Hindrance of Adaptation of Organism (CHAOS) that involve using CRISPR to target several genes in E.coli. Usually, the antibiotics target and act on only one or few genes, and thus, the bacteria soon get resistant to it. While in CHAOS technique manipulates several genes at the same time, therefore, bacterium began to lose its ability to survive, and it dies.

Research by University of Wisconsin, Madison

Researchers under the supervision of Jan Peter Van Pijkeren from the University of Wisconsin, Madison developed a CRISPR-based probiotic to make antibiotic resistant bacteria self-destruct mainly Clostridium difficile. They proposed by using CRISPR enclosed in bacteriophage, along with probiotics, will be taken by patients. Once bacteriophage reaches its target will release CRISPR, and thus, will force Clostridium difficile to cleave itself.

Research by Tel Aviv University

In 2015, a similar approach developed by Udi Qimron of Tel Aviv University. They used bacteriophage to deliver CRISPR along with probiotics; thus, sensitize antibiotics resistance bacteria to the drugs.

Department of Biological Sciences, the University of Texas at Dallas

Research published by the Department of Biological Sciences, the University of Texas at Dallas entitled “CRISPR-mediated removal of antibiotic resistance genes in Enterococcus faecalis populations”. They discussed one of the multi-drug resistant strain – ‘’Enterococcus faecalis’’, currently almost no antibiotics works on them. CRISPR/cas9 can be a viable option for treating this issue.

E. faecalis transfer their resistivity genes via plasmids horizontally. Moreover, MDR strains of E. faecalis modify them in such a way that their defense system does not attack these plasmids carrying antibiotic resistant genes. While, in fact, allow them to be integrated into their genome. By doing so, they weaken their defense system.

According to this study, researchers suggested that by designing CRISPR in such manner to re-activate the MDR E. faecalis defense system. So, that they won’t allow the uptake of foreign plasmids containing resistant genes.

CRISPR antibiotics resistance
CRISPR-Cas9 sequence targeting.

Companies Involved

Locus Biosciences

In 2019, Locus biosciences and Johnson & Johnson’s division, Janssen Pharmaceuticals signed a deal of $818 million. To develop CRISPR, that will target pathogenic and antibiotic-resistant bacteria, in the hope of overcoming antibiotic resistivity pandemic.

Eligo Biosciences

Eligo biosciences are also using CRISPR against antibiotic-resistant pathogens. They are aiming to use CRISPR to target human gut pathogens that are responsible for quite a large number of deaths and illnesses annually.

Eligo biosciences model involves first to remove/deactivate bacteriophage natural components followed by insertion of CRISPR components that will target specific gut pathogens.

Future Perspective

Search for new antibiotics is the most important goals of our time. However, scientists are thinking outside the box and looking for alternative approaches such as CRISPR gene editing technology. Hopefully, in the near future, CRISPR would be used to tackle antibiotics resistivity problem.

Explore More: 11 Diseases CRISPR Technology Could Cure!

 

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