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New 'shapeshifting' antibiotics could help combat drug-resistant superbugs

Infections that resist antibiotics.
Infections that resist antibiotics. Copyright Canva
Copyright Canva
By Oceane Duboust
Published on Updated
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Tens of thousands of people die every year from antibiotic-resistant infections. 'Shapeshifting' antibiotics could be the key to stopping it.

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Antimicrobial resistance is a growing problem, one the World Health Organization (WHO) declared "one of the top 10 global public health threats facing humanity".

In EEA countries - EU member states, Iceland and Norway - more than 35,000 people die each year from antibiotic-resistant infections, according to the European Centre for Disease Prevention and Control (ECDC).

But scientists are working to tackle the issue. A study published in early April shows promising results regarding new "shapeshifting" antibiotics.

Shapeshifting molecules

The new research is based on an already known and used molecule: vancomycin, an antibiotic used since the 1950s.

Despite being less common than penicillin and its by-products, some bacteria became progressively resistant to vancomycin, leading to the development of two new versions with the last one being in 2017.

To stop this race against time, researchers from the Cold Spring Harbour Laboratory in New York, the US, created a molecule that can shapeshift; in this case, the researchers behind have found a way to rearrange its atoms.

Click chemistry allows us to take very complicated molecules (such as the antibiotic vancomycin) and rapidly connect them together, much like how Lego pieces 'click' together.
Professor John E Moses
Study lead author

We should think of molecules as having one shape, that "allows drug molecules to interact very closely with the shape of a therapeutic target to cure cancer or treat a bacterial infection," similar to a key in a lock, the study’s lead author Professor John E Moses explained to Euronews Next.

In this comparison, a resistant bacteria is the equivalent of a new "lock" for which a new key must be made, a process that "can take a lot of time and money," he added.

His team combined vancomycin with a molecule called bullvalene, the latter having the ability to change its form. This makes it a fluxional - or non-rigid - molecule, something Moses came across while attending a conference in Australia in 2017.

"This ability to change shape rapidly can allow the drug molecules (the 'key') to still interact with the therapeutic target (the ‘lock’) even if its structure changes," Moses said.

Using click chemistry methods

To combine the two molecules, the team used click chemistry, a method for which Carolyn Bertozzi, Morten Peter Medal, and Karl Barry Sharpless won the Nobel Prize for Chemistry last year.

Simple, fast and efficient, click chemistry is beneficial for drug discovery as it preserves the specific properties of the molecules, in this case, the ability to kill bacteria.

"Click chemistry allows us to take very complicated molecules (such as the antibiotic vancomycin) and rapidly connect them together, much like how Lego pieces 'click' together. The chemistry is robust and reliable and works every time," Moses - who studied under Nobel laureate Sharpless - told Euronews Next.

The team - in collaboration with Dr Tatiana Soares da-Costa from the University of Adelaide - then tested the new combined molecule on wax moth larvae. The larvae were then infected with pathogen bacteria resistant to classic antibiotics.

The study, which was published in Proceedings of the National Academy of Sciences, showed the promising results of this shapeshifting antibiotic.

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By changing its shape, the drug was found to be effective against resistant pathogens. In addition, the bacteria did not develop a resistance to the new molecule which could keep working for longer than its previous counterparts.

The study’s authors underlined that the results could "offer a potential near to short-term solution that takes advantage of established supply chains and clinical success".

In addition to the global health benefits, this solution could also be economical as antibiotic resistance is estimated to cost €1.5 billion a year in Europe alone.

The team said that they were "paving the way for future studies" on the subject. The Cold Spring Harbor Laboratory is working currently to adapt this technique to other clinically-used antibiotics.

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"If we can invent molecules that mean the difference between life and death, that’d be the greatest achievement ever," said Moses.

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