Navigation Links
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 nd to the bacteria to such a degree that the loss of antimicrobial activity is reduced nearly 1,000 fold, Boger said.

In the study, the scientists developed two different re-engineered antibiotics and compared them in an antimicrobial assay against VanA, a strain of the bacteria that is highly resistant to treatment by glycopeptide antibiotics, including vancomycin and teicoplanin (a somewhat newer drug similar to vancomycin). Both showed a significant increase in binding ability-roughly 40 times more potent than today's version of the drug. The actual re-engineering was extremely challenging, Boger said, requiring not only a detailed molecular level understanding of the origin of the vancomycin resistance but a total of 24 sequential chemical steps to prepare the new antibiotics; in this case, a single atom in vancomycin was altered to counter an analogous single atom change in the bacterial cell wall that accounts for the resistance.

The results, Boger added, suggest that no matter how the VRE altered the cell wall component, it was still sensitive to treatment by the re-engineered vancomycin analogues.

"The complex chemical synthesis of the glycopeptide antibiotics was developed with the specific idea that this breakthrough technology could be used to alter and enhance their therapeutic properties," Boger said. "We hope that our pioneering efforts will spur further research into the development of more potent antibiotics."


'"/>

Source:Scripps Research Institute


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists find missing enzyme for tuberculosis iron scavenging pathway
5. Scientists seek answers on what activates deadly anthrax spores
6. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
7. Scientists collaborate to assess health of global environment
8. Scientists decipher genome of fungus that can cause life-threatening infections
9. Scientists discover the cellular roots of graying hair
10. Scientists rid stem cell culture of key animal cells
11. Scientists develop new color-coded test for protein folding
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... -- The Allen Institute for Cell Science today announces the ... and dynamic digital window into the human cell. The ... of deep learning to create predictive models of cell ... growing suite of powerful tools. The Allen Cell Explorer ... available resources created and shared by the Allen Institute ...
(Date:4/3/2017)... WASHINGTON , April 3, 2017 /PRNewswire-USNewswire/ ... single-cell precision engineering platform, detected a statistically ... cell product prior to treatment and objective ... highlight the potential to predict whether cancer ... prior to treatment, as well as to ...
(Date:3/29/2017)... -- higi, the health IT company that operates the largest ... , today announced a Series B investment from BlueCross ... new investment and acquisition accelerates higi,s strategy to create ... health activities through the collection and workflow integration of ... and secures data today on behalf of over 36 ...
Breaking Biology News(10 mins):
(Date:9/19/2017)... ... September 19, 2017 , ... The latest generation of ... of sample prep for metals digestion—the addition of acids and reagents. The accessory ... The system is ideal for any laboratory performing their own unique metals digestion ...
(Date:9/19/2017)... , ... September 19, 2017 , ... VetStem Biopharma ’s CEO and founder, Dr. ... PhD in Riordan’s new book "Stem Cell Therapy: A Rising Tide". Dr. Harman and ... They bonded over an interest in the potential of stem cell therapy and a ...
(Date:9/19/2017)... -- ValGenesis Inc., the global leader in Enterprise Validation ... strategic partnership with VTI Life Sciences (VTI). This partnership ... the latest technology available in the ValGenesis VLMS system. ... and cost-effective validation services using ValGenesis VLMS. VTI will ... system. The partnership ...
(Date:9/19/2017)... ... September 19, 2017 , ... ... Financial Services (NYS DFS) cybersecurity regulations have transitioned into full force ... organizations operating in the state (“Covered Entities”) to conduct an annual, professional, ...
Breaking Biology Technology: