Antibiotic resistance

Six grand ideas to fight the end of antibiotics

Overuse of antibiotics has led them to becoming less and less effective to treat us when we’re sick – leaving scientists scrambling for a fix. Here are some of the best ideas to tackle one of the 21st Century's biggest challenges.

The world is nearing a moment when antibiotics no longer work to treat infections. We are severely over-using the antibiotics we have – and that system is causing bacteria to evolve and develop resistance to the drugs intended to kill them.

Appropriately, the phenomenon is referred to as antibiotic resistance, and it’s shaped up to be one of the biggest challenges we face in the 21st Century.

The stakes are high. The good news? A whole slew of governments, organisations, innovators, and scientists across the globe is pondering how to get us out of this mess. Here are just a few of the many methods being employed in the fight against antibiotic resistance.

USING BACTERIA AGAINST ITSELF

If drugs fail, why not fight fire with fire?

Several new biotech companies are hoping to use our growing understanding of the human microbiome: healthy microbes that live in the human body, which boost our immune system, prevent infection, and regulate metabolism. It could help develop a new class of drugs that fight superbugs – infections resistant to drugs, expected to kill more people than cancer by 2050.

We are severely over-using the antibiotics we have

Vedanta Biosciences, based in Cambridge, Massachusetts, is one firm basing its drug development on the new thought that many bacteria may cause infection because the patient has depleted their own microbiome through overuse of antibiotics. Vedanta is using research conducted on the microbiome around the world to identify good bacteria that they can put in pill form – a swallowable solution that will then enter the gut and stimulate immune response.

“Microbiome-based therapies such as bacterial consortia are a much-needed alternative to antibiotics. It is important to look for new ways to treat infection that are both less prone to eliciting resistance and do not damage the microbiota and thus render the host vulnerable to reinfection,” says Bernat Olle, Vedanta CEO.

It is important to note, however, that scientists still do not fully understand the human microbiome. But research into how it works is moving at a quick pace and Vedanta is nearing the clinical trial stage for at least two of its drugs. If they work, it could be a game-changer for fighting infections.

DEPLOYING TINY SEMICONDUCTORS

This idea comes from researchers at the University of Colorado, Boulder, who were working on developing quantum dots for use in harnessing solar energy to make fuel. What are quantum dots? Small crystals of semiconductors – the material we use to make phones and computers. (Small is an understatement. As Prashant Nagpal, a UC researcher on the project says: “A quantum dot is to the width of a hair roughly what a city block is to the Earth.”)

Together with colleague Anushree Chattetrjee, who works on developing new therapies for antibiotic treatment, Nagpal wondered if the light-responsive dots could be used to fight superbugs. The result was a new form of quantum dots that can selectively target bacteria.

“What it could mean is that these quantum dots can be present everywhere, and when developed completely as a therapy, they can be activated by light to clear infections in animals or humans without killing the host mammalian cells,” Nagpal says. When activated, the dots produce just enough a substance that is toxic to bacterial cells, but harmless to the host’s own cells.

When testing the dots in cell cultures, the dots had no effect on healthy human cells. And light exposure to activate them could be as little as a room light or the sun (or a more directed LED for deeper infections).

They could theoretically be so effective, that they would only require a one million-times smaller dose than traditional drugs.

Quantum dots are easily and cheaply manufactured so scaling them up to treat infections on a worldwide scale would cost just a few cents (or less) per dose.

“A minuscule amount of drug with some light can treat some of the worst superbug infections we tested in clinical strains acquired from a Colorado hospital,” Nagpal says. “Of course, more work and extensive studies in preclinical and clinical trials need to be done before we can administer these quantum dots to patients. However, this initial study shows a lot of promising features.”

INFECTION-KILLING POLYMERS

Antibiotics may not be the only answer to fighting superbugs. Researchers at the University of Melbourne have discovered a totally unconventional method of killing deadly bacteria.

Turns out a star-shaped polymer (a chain of molecules) that they engineered 15 years ago to add viscosity to automotive paints and engine oils has some interesting abilities when it’s re-purposed for biological uses. While researching the polymer’s ability to deliver drugs to treat cancer, the scientists realised that a version of the star called Snapp (Structurally Nanoengineered Antimicrobial Peptide Polymers) had become toxic to bacteria.

Among other ways of killing the bugs, it has the ability to rip apart their cell walls by becoming absorbed into the cell’s membrane and pulling out its lipid layer.

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If funding comes through, the researchers think they could be testing this method in humans within five years. “Our star synthesis is an engineering process and can be easily scaled up. It is also not very expensive. The regulatory approval will likely be the slowest step,” says chemical engineer Greg Qiao, whose lab at the Melbourne School of Engineering is responsible for the work.

GETTING OUT OF SILOES

One of the biggest problems in medicine, and science in general, is that researchers don’t always work directly with doctors to solve health problems. That means they tend to miss out on key data that can only be gleaned by working directly with patients.

At the Antibiotic Resistance Center at Emory University in Georgia, clinicians and research scientists are working together to better understand how to diagnose and treat resistance. “I’m not a doctor. I need to know from the clinicians a lot of what they’re seeing on the front lines to help guide our research to be as relevant as possible,” says David Weiss, director of the center.

One of the biggest results of this partnership so far has been the development of a new diagnostic test to help doctors discover what bacterium is responsible for resistance inside a patient that’s not responding to antibiotics. Based on the success of this model, Weiss says, other clinical institutions are starting to open their own versions of the centre that brings researchers and doctors together.

BRIDGING ACADEMIA AND INDUSTRY

The world desperately needs new antibiotics, but drug companies haven’t developed a new one in 30 years. That’s because drug development is extremely expensive and there’s little profit in the final product.

To address this, Pew Charitable Trusts, a public policy non-profit in Philadelphia, has developed the Shared Platform for Antibiotic Research and Knowledge (Spark). It’s a cloud-based, virtual library of antibiotic research data and analytics that scientists can use to work together on building new discoveries. “Similar data-sharing resources have successfully catalysed drug discovery in other research areas such as cancer, neglected tropical diseases, and tuberculosis,” says Kathy Talkington, director of the antibiotic resistance programme at Pew Charitable Trusts. “We hope that Spark will do the same for antibiotic-resistant bacteria. We expect it to be publicly available, and open for use by researchers from around the world, within the next year.”

The hope is that allowing scientists to work across different disciplines, develop new methodologies for antibiotic discovery, and work within academia and the industry could be the key to ending the years-long drought in new antibiotic development.

One of the biggest problems in medicine, and science in general, is that researchers don’t always work directly with doctors to solve health problems

The US Centers for Disease Control (CDC) is also responding to the problem with a network of their own. Specifically, the Antibiotic Resistance Lab Network, which was developed in 2016, is boosting the organisation’s ability to detect antibiotic resistance whenever it shows itself – whether that be in healthcare, food, or community settings.

With labs strategically placed around the United States, it tracks resistance trends and shares data with hospitals, doctors, and scientific institutions developing diagnostic tests and new treatments. In addition to these core labs, the CDC laboratories in all 50 states received additional funding to genetically test for a series of antibiotic resistant bacterium.

It’s a nationwide effort that pits knowledge and teamwork against the growing health crisis of antibiotic resistance.

“The Antibiotic Resistance Laboratory Network (ARLN) increases our ability to detect and identify new resistant threats in the United States,” says Jean Patel, the science team lead of the Antibiotic Strategy and Coordination Unit. “Laboratories in this network are focusing on specific germ-testing that provides essential information to stop the spread of resistant infections.”

MAKING EXISTING ANTIBIOTICS STRONGER

Finally, one antibiotic, called vancomycin, has been used to treat infections for at least 60 years. It is considered a “last-resort” drug, used only when there are no other options, because it has avoided antibacterial resistance – until now.

In recent years bacteria resistant to the drug have been discovered. In response to this scientists have been attempting to re-engineer the antibiotic to make it more powerful and more effective. They do this by changing its structure. So far there have been three modifications to the drug by scientists over the years. The most recent two, carried out by Dale Bolger and his team at the Scripps Research Institute in La Jolla, California, added additional mechanisms for the antibiotics to kill bacteria.

“Each improved potency and each improved their durability toward resistance,” says Bolger. And resistance to the new strain, he says, will be much, much slower to develop. The first modification alone is “robust and could alone last 50 years in clinic. If bacteria devise a way to get around it they are still killed by the other two mechanisms and resistance would fail to propagate.” Work is currently being done to make the new version of the drug less complicated to manufacture.

But Bolger says it is “exciting.” Eventually, having a reliable last-resort drug that is difficult for bacteria to resist could save many lives.

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Whether it’s stronger drugs, bacteria-shredding polymers, confoundingly small semiconductors, or something new entirely – it’s a promising sign that scientists are staying busy generating grand ideas to solve what could be humanity’s biggest health problem of the modern era.