Shape-shifting antibiotics: The newest weapon against deadly infections
[Apr. 7, 2023: JD Shavit, The Brighter Side of News]
Drug-resistant bacteria and fungi have become a major public health threat worldwide, killing 35,000 people annually in the US alone.. (CREDIT: Creative Commons)
Drug-resistant bacteria and fungi have become a major public health threat worldwide, killing approximately 35,000 people in the United States alone each year. Antibiotics have been essential in fighting infections, but overuse has led to certain bacteria developing resistance to them.
As a result, treating these infections has become challenging, and the World Health Organization has classified antibiotic resistance as a top ten global public health threat.
Now, Professor John E. Moses at Cold Spring Harbor Laboratory (CSHL) has developed a new weapon against these drug-resistant superbugs – an antibiotic that can shape-shift by rearranging its atoms. This revolutionary development could potentially be the key to our species’ survival and evolution.
Moses came up with the idea of shape-shifting antibiotics while observing tanks in military training exercises. The tanks' rotating turrets and nimble movements allowed them to respond quickly to possible threats.
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A few years later, Moses learned of a molecule called bullvalene. Bullvalene is a fluxional molecule, meaning its atoms can swap positions, giving it a changing shape with over a million possible configurations – exactly the fluidity Moses was looking for.
Several bacteria, including MRSA, VRSA, and VRE, have developed resistance to vancomycin, a potent antibiotic used to treat everything from skin infections to meningitis. Moses thought he could improve the drug’s bacteria-fighting performance by combining it with bullvalene.
He turned to click chemistry, a Nobel Prize-winning class of fast, high-yielding chemical reactions that “click” molecules together reliably. This makes the reactions more efficient for wide-scale use. Moses and his colleagues created a new antibiotic using this technique, with two vancomycin “warheads” and a fluctuating bullvalene center.
Moses and Dr. Tatiana Soares da-Costa of the University of Adelaide tested the new drug on VRE-infected wax moth larvae, which are commonly used to test antibiotics. They found the shape-shifting antibiotic significantly more effective than vancomycin at clearing the deadly infection. Additionally, the bacteria did not develop resistance to the new antibiotic.
The chemical structure of the new antibiotic was designed by Moses and synthetically assembled by his lab. Dr. Thomas Fallon, Moses’ collaborator at the University of Newcastle, Australia, provided the shape-shifting bullvalene core. Moses says one commenter called the study “probably the ‘coolest’ and most complex natural product derivative paper I’ve come across.” (CREDIT: Moses lab/Cold Spring Harbor Laboratory)
Moses believes that this discovery has significant implications for the future of medicine. Researchers can use click chemistry with shape-shifting antibiotics to create a multitude of new drugs. Such weapons against infection may even be key to our species’ survival and evolution.
"If we can invent molecules that mean the difference between life and death," Moses says, "that'd be the greatest achievement ever."
The rise of drug-resistant bacteria and fungi has been a growing concern for healthcare professionals worldwide. According to the Centers for Disease Control and Prevention (CDC), antibiotic-resistant bacteria cause at least 2.8 million infections and 35,000 deaths each year in the United States alone.
Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. (CREDIT: PNAS)
One of the main reasons for this increase in antibiotic resistance is the overuse and misuse of antibiotics. When antibiotics are used to treat viral infections, they are ineffective. Moreover, overprescribing antibiotics and using them in animal feed has led to the development of drug-resistant bacteria. This problem is not unique to the United States. It is a global concern that requires immediate attention.
Moses and his team at Cold Spring Harbor Laboratory hope that their discovery will help combat this problem. The new antibiotic they have created has the potential to change the way we treat infections. It could be the beginning of a new era in medicine, one in which antibiotics are not the only solution.
Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. (CREDIT: PNAS)
The idea of shape-shifting antibiotics is not entirely new. Researchers have been working on similar concepts for years. Still, Moses's discovery is unique because of the use of bullvalene. The molecule's ability to rearrange its atoms gives the antibiotic the flexibility it needs to adapt to the changing bacterial landscape. This is particularly important in the fight against drug-resistant superbugs, which can evolve rapidly and unpredictably.
By combining the stability and potency of vancomycin with the shape-shifting properties of bullvalene, Moses has created a powerful new tool in the battle against antibiotic resistance. The potential applications of this breakthrough are vast, and researchers are eager to explore the many possibilities.
With continued innovation in the field of antibiotic research, we may yet find a way to stay one step ahead of the evolving superbugs.
For more science and technology stories check out our New Discoveries section at The Brighter Side of News.
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