Strategic Communications and Marketing News Bureau

New compound overcomes drug-resistant Staph infection in mice

CHAMPAIGN, lll. – 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.

Read Next

Humanities Diptych image with book cover of "The New Internationals" and a headshot of English professor David Wright Faladé

English professor’s novel tells of love triangle in post-WWII Paris, based on his family history

CHAMPAIGN, Ill. — A new novel by University of Illinois Urbana-Champaign English professor David Wright Faladé tells the story of three people in a love triangle in post-World War II Paris. The characters in “The New Internationals” — a young French woman who has survived the Holocaust, a university student from West Africa and a […]

Life sciences Portrait of the research team posing together.

Minecraft players can now explore whole cells and their contents

CHAMPAIGN, Ill. — Scientists have translated nanoscale experimental and computational data into precise 3D representations of bacteria, yeast and human epithelial, breast and breast cancer cells in Minecraft, a video game that allows players to explore, build and manipulate structures in three dimensions. The innovation will allow researchers and students of all ages to navigate […]

Arts Photo of seven dancers onstage wearing blue tops and orange or yellow flowing skirts. The backdrop is a Persian design.

February Dance includes works experimenting with live music, technology and a ‘sneaker ballet’

CHAMPAIGN, Ill. — The dance department at the University of Illinois Urbana-Champaign will present February Dance 2025: Fast Forward this week at Krannert Center for the Performing Arts. February Dance will be one of the first performances in the newly renovated Colwell Playhouse Theatre since its reopening. The performances are Jan. 30-Feb. 1. Dance professor […]

Strategic Communications and Marketing News Bureau

507 E. Green St
MC-426
Champaign, IL 61820

Email: stratcom@illinois.edu

Phone (217) 333-5010