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New Strategy Cracks Staph Bacterium's "Golden Armor"

A team of researchers, including staff at Cedars-Sinai, has exploited a structural vulnerability in Staphylococcus aureus that in laboratory experiments and a mouse study opened the "superbug" to treatment with an anti-cholesterol medication. This follows the 2005 discovery that a pigment provides a "golden armor" that enables staph to evade the immune system.

A February 14 article published in the online version of Science (Science Express) describes the study, which was conducted by researchers at Cedars-Sinai Medical Center, the National Taiwan University in Taipei, the University of Illinois at Urbana-Champaign and the University of California, San Diego.

After treatment with the drug, staph bacteria were about 15 times more susceptible to killing by hydrogen peroxide and were four-fold less able to survive in human blood, according to George Y. Liu, M.D., Ph.D., one of the article's co-first authors. Dr. Liu directs a laboratory focusing on staph aureus research at CSMC's Immunobiology Research Institute and serves as an assistant professor of pediatrics at the medical center.

In a study of systemic staph infection, the researchers found a 50-fold decrease in bacteria in laboratory mice treated with the drug, said Dr. Liu.

Pictured at right: Staphylococcus Aureus infection

In 2005, Dr. Liu and other researchers discovered that a pigment giving staph aureus cells their yellow-orange color actually fend off key immune system cells. Neutrophils and macrophages kill most bacteria, but staphyloxanthin, the staph aureus pigment, neutralizes their bacteria-killing chemicals.

"Initially, we were intrigued by this color and the pigment, which is a carotenoid pigment, similar to betacarotene found in tomatoes, carrots and bright-colored vegetables. We wondered if this carotenoid pigment could be protecting staph aureus from neutrophils and macrophages of the immune system," said Dr. Liu, first author of the 2005 article that appeared in the Journal of Experimental Medicine. At the time, he was a senior research fellow at UCSD, working with Victor Nizet, M.D., professor of pediatrics and pharmacy, who was also involved in the new study.

After publication of the original "golden armor" study, Dr. Liu and Dr. Nizet were contacted by Eric Oldfield, Ph.D., professor of chemistry and biophysics at the University of Illinois, who recruited Andrew Wang, Ph.D., and other specialists in Taiwan to help study the crystal structure of the pigment-producing enzyme.

The researchers found that not only were the initial steps similar, but a drug designed to block the activity of the cholesterol-producing enzyme also was capable of binding to and interrupting the staphyloxanthin-related enzyme. Stripped of its golden pigment, staph aureus became open to attack by immune system cells and bacteria-killing chemicals such as hydrogen peroxide.