New antibiotic could eliminate the global threat of antibiotic-resistant infections

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Modified vancomycin antibiotic (credit: Akinori Okano et al./PNAS)

Scientists at The Scripps Research Institute (TSRI) have discovered a way to structurally modify the antibiotic called vancomycin to make an already-powerful version of the antibiotic even more potent — an advance that could eliminate the threat of antibiotic-resistant infections for years to come.

“Doctors could use this modified form of vancomycin without fear of resistance emerging,” said Dale Boger, co-chair of TSRI’s Department of Chemistry, whose team announced the finding Monday (May 29, 2016) in the journal Proceedings of the National Academy of Sciences.

“The death of a hospitalized patient in Reno Nevada for whom no available antibiotics worked highlights what World Health Organization and other public-health experts have been warning: antibiotic resistance is a serious threat and has gone global,” KurzweilAI reported in January 2017. The new finding promises to lead to a solution.

First antibiotic to have three independent mechanisms of action

Vancomycin  has been prescribed by doctors for 60 years, and bacteria are only now developing resistance to it, according to Boger, who called vancomycin “magical” for its proven strength against infections. Previous studies by Boger 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,” Boger said.

The new study shows that scientists can now make a third modification that interferes with a bacterium’s cell wall in a new way, with promising results. Combined with the previous modifications, this alteration gives vancomycin a 1,000-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,” said 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; the current method takes 30 steps.

The study was supported by the National Institutes of Health.

from KurzweilAI » News http://ift.tt/2rrKC54

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