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Scientists Supercharge Powerful Antibiotic

2017-05-31
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Scientists at The Scripps Research Institute (TSRI) have tweaked a powerful antibiotic, called vancomycin, so it is once more powerful against life-threatening bacterial infections. Researchers say the more powerful compound could eliminate the threat of antibiotic resistance for many years to come.




“Doctors could use this modified form of vancomycin without fear of resistance emerging,” said Dale Boger, Ph.D., co-chair of TSRI’s department of chemistry, whoseteam announced the finding (“Peripheral Modifications of [Ψ[CH2NH]Tpg4] Vancomycin with Added Synergistic Mechanisms of Action Provide Durable and Potent Antibiotics”) in Proceedings of the National Academy of Sciences.


Dr. Boger called vancomycin “magical” for its proven strength against infections. Previous studies by him and his colleagues at TSRI had shown that it is possible to add two modifications to vancomycin to make it even more potent. “With these modifications, you need less of the drug to have the same effect,” he pointed out.


The current study shows that scientists can make a third modification–which interferes with a bacterium’s cell wall in a new way–with promising results. Combined with the previous modifications, this alteration gives vancomycin a 1000-fold increase in activity, meaning doctors would need to use less of the antibiotic to fight infection.


The discovery makes this version of vancomycin the first antibiotic to have three independent mechanisms of action. “This increases the durability of this antibiotic,” continued Dr. Boger. “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”


Tested against enterococci bacteria, the new version of vancomycin killed both vancomycin-resistant enterococci and the original forms of enterococci.The next step in this research is to design a way to synthesize the modified vancomycin using fewer steps in the lab, as the current method takes 30 steps. But Dr. Boger calls this the “easy part” of the project, compared with the challenge of designing the molecule in the first place.

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