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Scientists re-engineer a well-known antibiotic to counter drug resistance

The scientists replaced a single atom from the molecular structure of vancomycin aglycon, a glycopeptide antibiotic that attacks the bacteria by inhibiting cell wall synthesis, significantly increasing the drug's spectrum of activity. In recent years, a number of the most common strains of enterococci have become resistant to vancomycin and use of the antibiotic has been under scrutiny. This re-engineering effort could help make the drug more effective in treating infections produced by vancomycin resistance enterococci (VRE), a serious and growing problem in the nation's hospitals.

While several antibiotics target a bacterium's cell wall, vancomycin binds to a specific component of this wall. Drug resistance results when the VRE actually alters these cell-wall components, interfering with the drug's ability to bind to the bacterium. According to the Centers for Disease Control, VRE were first reported in 1986, nearly 30 years after the introduction of the drug. The study, published in the Journal of the American Chemical Society, was conducted by Brendan M. Crowley, Ph.D. candidate at Scripps Research's Kellogg School of Science and Technology, and Professor Dale L. Boger of the Scripps Research Department of Chemistry and The Skaggs Institute for Chemical Biology.

"The continued rise of vancomycin-resistant infection poses a serious threat to hospital patients in the U.S. and around the world," Boger said. "These infections not only increase the length of hospital stays, but they raise patient mortality rates as well. Our successful synthesis of a novel vancomycin analogue with a molecular structure that restores much of the drug's binding ability could potentially lead to the development of a new generation of antibiotics that could prove far more effective against vancomycin-resistant infections than what is available today."

The most common strains of VRE-called VanA and VanB-are both capable of inhibiting the antibiotic's ability to bi
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Source:Scripps Research Institute


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