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.
University of Illinois at Urbana-Champaign: http://www.uiuc.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
A riverside in Nebraska is a welcome refuelling stop for these elegant birds migrating from Mexico to their breeding grounds
Deprived of sight, blind people manage to squeeze an amazing amount of information out of their other senses. Doing this requires their brains to do some reorganizing. To learn about some of these changes, scientists studied the brains of blind people ...
In 1973, American soldiers on the Mekong River in Laos killed and hauled ashore a massive 24-foot ribbon of a fish. It was the “Queen of the Naga,” claimed a postcard still widely circulated in Southeast Asia with the above ...
Bald eagles have made a comeback. See life in the nest now during peak nesting season.
Photos capture a river otter attacking a gator in a Florida river. The otter then feasted, witnesses say.
The 10-meter long Torvosaurus weighed up to five tons.
Researchers say the key to fighting superbugs is individualized treatment plans, and a new nanochip might pave the way
Some farmers have long sworn by mellow tunes to boost Bessie's milk production. The science is hardly conclusive. But a study hints at what might top the barnyard playlist. (Psst: They liked R.E.M.)
Craig Venter, the U.S. scientist who raced the U.S. government to map the human genome over a decade ago and created synthetic life in 2010, is now on a quest to treat age-related disease.
Dr Dave Hone: The Daohugou Fauna is rich in dinosaurs, lizards, pterosaurs, salamanders and mammalsDr Dave Hone