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 HKUST researchers discover ways to regenerate corticospinal tract axons
06.07.2015 | Hong Kong University of Science and Technology

nachricht Southampton researchers go with the flow to help protect endangered European eel
06.07.2015 | University of Southampton

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Aluminum Clusters Shut Down Molecular Fuel Factory

06.07.2015 | Power and Electrical Engineering

Veja Mate Offshore orders 67 wind turbines including record long-term service

06.07.2015 | Press release

The quantum middle man

06.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>