Did someone call the superbug exterminator?

Yichi Zhang
6 July 2015

Above: Diagram of the possible mechanism for CRISPR (Wikimedia Commons/James atmos)

Superbugs are bacteria that are resistant to most known antibiotics, and they are causing big problems around the world. For example, the superbug New Delhi metallo-beta lactamase 1 (NDM1), named after the city where its genetic code was first identified, has infected large numbers of people in India, France, Japan, and the United States. This particular drug-resistant bacteria has also infected 18 people in Canada. In India alone, superbug infections have killed up to 58,000 infants annually in the past few years. Clearly, superbugs are not harmless pests.

Did you know? Any bacteria can become superbugs by exchanging genes with existing drug-resistant bacteria.A good exterminator needs powerful tools that kills the right pests without killing or harming anything else. To deal with drug-resistant bacteria, scientist-exterminators have developed a powerful tool using clustered regularly interspaced short palindromic repeats (CRISPRs) that could spell the end for superbugs once and for all! A second tool, called Combination Genetics En Masse (CombiGEM), supports efforts to fight resistant bacteria using both antibiotics and CRISPRs.

Of course, it is also important to prevent the development and spread of superbugs by not using antibiotics to treat viral infections. Antibiotics will have no effect on the virus making you sick, but they will destroy good bacteria in your body and potentially help make others resistant to antibiotics. Recently, the United States issued specific recommendations on how to combat the spread of antibiotic resistance. They include improving the surveillance of superbugs and encouraging the development of new tools for fighting bacterial infections.

CRISPRs provide one of these tools. In fact, you might say the tool was originally developed by bacteria themselves! Long before scientists began trying to use CRISPRs to fight drug-resistant bacteria, bacteria were using them to fight off attacks from other microorganisms, including bacteriophage viruses.

Before bacteria had CRISPRs, invading viruses could easily insert their own DNA into the bacteria, using their host to produce more copies of the viral DNA. This was a huge weakness of bacteria, like the hole in the middle of the Deathstar, with Luke Skywalker as the bacteriophage virus ready to destroy it!

However, bacteria eventually developed a way of defending themselves against these viruses by cutting the foreign DNA at specific sites. CRISPRs are short, repetitive sequences of DNA that produce RNA strands that are complementary to the viral DNA, identifying where to cut and preventing the foreign DNA from inserting itself into the bacterial DNA.

Meanwhile, bacteria that are resistant to specific antibiotics have genes that code for proteins that protect them. For example, extended-spectrum beta-lactamases (ESBLs) are enzymes produced by one category of bacteria that protect the bacteria from penicillin and other antibiotics using hydrolysis. In other words, they cause the antibiotics’ chemical bonds to break down in the presence of water.

Did you know? Bacteria evolved to use CRISPRs to fight off viruses. Now, scientists have begun to harness CRISPRs as a method for fighting antibiotic resistant superbugs.Recent research into CRISPRs has provided a way of selectively deleting genes that make bacteria antibiotic resistant, brilliantly turning bacteria’s defence mechanism against them. In particular, scientists at the Massachusetts Institute of Technology (MIT) have successfully created DNA sequences that selectively target and cut superbug DNA so that superbugs lose the power to destroy and resist antibiotics. By removing these genes, the drug-resistant bacteria are transformed from dangerous and relentless superbugs to weak and relatively harmless pests that can be killed by the next round of antibiotics.

Even though it is an effective way to kill superbugs, the CRISPR technique is very expensive to use. It takes a lot of time and resources to design individual CRISPR sequences to target the large number of drug-resistant genes that different bacteria possess. So scientist-exterminators are constantly trying to find cheaper and more effective tools.

For example, researchers at MIT have developed another tool called CombiGEM. It essentially mixes and matches DNA sequences from various superbugs and normal bacteria found in the same patient. By identifying specific gene combinations, this technique makes it possible to select the antibiotics that are best equipped to kill specific bacteria. CombiGEM also identifies specific drug-resistant genes to cut using the CRISPR technique.

Despite the increasing prevalence of the drug-resistant bacteria called superbugs, scientists-exterminators have also been making great strides. Using CRISPRs, researchers have found a way using bacteria’s internal defence mechanism to remove the genes that provide superbugs with antibiotic resistance. Meanwhile, CombiGEM identifies DNA sequences that make superbugs more vulnerable to both the CRISPR technique and antibiotics.

Learn more!

CRISPR, the disruptor (2015)
Heidi Ledford, Nature 522

Battling superbugs (2014)
Anne Trafton, MIT News

Articles discussing the significance and potential of the CRISPR technique and CombiGEM.

Stop the Spread of Superbugs: Help Fight Drug-Resistant Bacteria (2014)
News in Health, US National Institutes of Health

Fecal transplants: The healing power of poo (2014)
Stefanie Vogt, CurioCity by Let’s Talk Science

Bacterial Resistance to Antibiotics (2008)
Kenneth Todar, Todar’s Online Textbook of Bacteriology

Articles discussing the development, spread and treatment of antibiotic-resistant superbugs.

Yichi Zhang

My name is Tony Zhang and I recently graduate with a B.ScH in Kinesiology from Queen's University in 2014. I am currently living at home in Ottawa and I have conducted research on human vascular function in response to stress, the regenerative abilities of zebrafish, the effect of aging on mitochondrial protein turnover in human muscle, intrinsic defects in the muscle of mice with a disease called spinal muscular atrophy, and currently, the role of a family of transcription factors called NFATs in muscle and cardiac tissue during metabolic rate depression in hibernating squirrel. I am rower on Carleton University's rowing team. Also, basketball, and sports in general have always been my number one passion because of all the valuable experiences and opportunities that it has given me. As a result, I chose to pursue a degree in Kinesiology at Queen's University with the goal of learning how to inspire, empower, and help others improve their physical health and well-being through sport and physical activity. 

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