Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New compound overcomes drug-reistant Staph infection in mice

08.01.2013
Researchers have discovered a new compound that restores the health of mice infected with methicillin-resistant Staphylococcus aureus (MRSA), an otherwise dangerous bacterial infection. The new compound targets an enzyme not found in human cells but which is essential to bacterial survival.

The research team, led by scientists at the University of Illinois and the University of California, San Diego, reports the new findings in the Proceedings of the National Academy of Sciences.

The team discovered and developed several compounds that are promising leads for antibacterial drug development, and the most potent was tested in mice infected with MRSA.

The rise of antibiotic-resistant bacterial infections is a global public health problem, said U. of I. chemistry professor Eric Oldfield, who led the research with UC San Diego professor Andrew McCammon.

“There’s an urgent need for more antibiotics because of drug resistance,” Oldfield said. “There are, for example, completely drug-resistant strains of tuberculosis. None of the drugs work against these strains of tuberculosis ,and so, if you get it, you die.”

Other infections, such as gonorrhea, which once were easily cured with antibiotics, also are becoming resistant to treatment, Oldfield said. “And Staph itself actually kills more people in the U.S. than does HIV/AIDS.”

To begin the study, McCammon and his colleagues at UC San Diego used computer simulations to look for potential chinks in the armor of a bacterial enzyme known as FPPS that aids in bacterial cell wall formation.

The researchers then screened libraries of small molecules to identify some that might target those sites and interrupt the activity of FPPS. Oldfield’s team tested some of these molecules against FPPS, but found that they were not particularly potent inhibitors of the enzyme.

“Then we tested the most promising compound against the next enzyme in the pathway, and we found that it was 20 times more active against that enzyme,” Oldfield said.

That enzyme, called UPPS, “is important because it’s involved in bacterial cell wall biosynthesis,” he said. “And a lot of the antibiotics that we have – drugs like penicillin, methicillin, vancomycin – all target bacterial cell wall biosynthesis.”

Graduate student Wei Zhu and research scientist Yonghui Zhang worked with Oldfield to develop and test new analogs of the compound that worked against UPPS.

“And we found one that was about 1,000 times more active than the first hit we had against FPPS,” Oldfield said.

Illinois chemistry and Institute for Genomic Biology professor Douglas Mitchell tested the new compound against regular and drug-resistant S. aureus in cell culture and found that it had potent activity against both.

“He also found that it augmented the effects of methicillin” in methicillin-resistant Staph strains, Oldfield said.

In a final test, Dr. Victor Nizet at UC San Diego used the new compound to treat mice infected with MRSA.

“Twenty out of 20 animals survived if they were treated with this drug lead and zero survived if they weren’t treated,” Oldfield said.

More years of study will be needed to determine whether this compound or others like it will be effective in humans, Oldfield said, but the findings may allow scientists to target multiple enzymes essential to bacterial survival, thus reducing the likelihood that new forms of drug resistance will emerge.

The National Institutes of Health, National Science Foundation and Howard Hughes Medical Institute supported this research.

Editor’s note: To reach Eric Oldfield, call 217-333-3374;
email eoldfiel@illinois.edu.
The paper, “Antibacterial Drug Leads Targeting Isoprenoid Biosynthesis,” is available online:

http://www.pnas.org/content/110/1/123.full?sid=7f30ce71-6679-46d9-bdd3-238386dd2efa

Diana Yates | University of Illinois
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

11 million Euros for research into magnetic field sensors for medical diagnostics

27.05.2016 | Awards Funding

Fungi – a promising source of chemical diversity

27.05.2016 | Life Sciences

New Model of T Cell Activation

27.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>