From: Reuters
Published February 15, 2008 02:49 PM

Cholesterol drug strips staph of color, virulence

By Deena Beasley

LOS ANGELES (Reuters) - Potentially deadly staph bacteria may be easily defeated by the body's own immune system once stripped of their golden hue by a drug developed to lower cholesterol, according to new research.

The findings offer a promising new direction in the fight against increasingly drug-resistant staph infections, according to the National Institutes of Health, which supported the research.

An international team of researchers found that a "squalene synthase inhibitor," originally developed by Bristol Myers Squibb, blocks infections of Staphylococcus aureus, named for its "golden halo," in mice.

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Staph contains a carotenoid -- like beta carotene in carrots -- that acts like an antioxidant against the immune system, Dr. Eric Oldfield, chemistry professor at the University of Illinois at Urbana-Champaign and the study's lead researcher, said in a telephone interview.

The body's circulatory system essentially puts out "bleach" to kill invaders, but staph's golden pigment blocks the process, he explained.

Observing research showing that removing a gene in staph's pigment-making pathway created a less virulent bacteria, Dr. Oldfield noticed that the metabolic pathway was similar to the one for the production of cholesterol in humans.

"Once you knock out the enzyme, the bacteria still proliferates, but the immune system can kill it," he said.

Other researchers discovered that three drugs designed to act on the human cholesterol enzyme blocked staph's pigment production in lab tests.

When they treated staph-infected mice with one of the compounds, dubbed BPH-652, the bacterial population was reduced by 98 percent. The results were published in the latest online edition of the journal Science.

A spokesman for Bristol-Myers said the company was no longer developing the compound, part of a class known as squalene synthase inhibitors, which has been largely surpassed by the popular cholesterol-fighting statin drugs.

"They would probably have adverse side effects if you took them for 40 years ... but that doesn't happen in one week," Dr. Oldfield said, referring to the likely treatment timeline for patients infected with staph, which largely occurs in hospitals.

He said the research team is testing several hundred other compounds "to see if we get something better."

Meanwhile, the next step will be to explore whether the pigment-fighting approach will work in humans.

"Although the results are still very preliminary, they offer a promising new lead for developing drugs to treat a very timely and medically important health concern," NIH Director Dr. Elias Zerhouni said in a statement.

Drug-resistant forms of staph have become more common, and in October a report in the Journal of the American Medical Association showed that methicillin-resistant Staphylococcus aureus killed an estimated 19,000 Americans in 2005.

(Reporting by Deena Beasley, Editing by Steve Orlofsky)

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