In the Feb. 14. 2008, issue of Sciencexpress, researchers reported on a new approach to vanquishing Staphylococcus aureus, a bacterium whose methicillin-resistant version is becoming a public health nightmare as new, nasty strains are popping up in community settings. (See BioWorld Today, Nov 12, 2007.)

S. aureus gets its last name from its color. In translation, the bug is called "Golden Cluster Seed." The bacterium makes a series of pigments that are red and orange, giving it its golden glow.

Which leads naturally to a question: "Why did staph bother to become golden? It's a bacterium - it's not like it has a fashion sense," Victor Nizet told BioWorld Today.

A few years ago, Nizet, who is an associate professor of pediatrics at the University of California, San Diego, and his colleagues showed why: staph is trying to pass itself off as a health benefit to the immune system.

The pigments' true beauty to the bug lies in their function: They are antioxidants, and one of them - which goes by the name staphyloxanthin and has structural similarities to beta-carotene - protects the bacterium from attack by the host's neutrophils.

Nizet's group also published the structure of several staphyloxanthin precursors. And when reading that paper, Eric Oldfield of the University of Illinois - who shares senior author credit with Nizet and Andrew Wang of the Academia Sinica in Taiwan on the current Science paper - realized that its structure was similar to an early precursor of cholesterol, and that compounds, which interfere early in the cholesterol synthesis pathway, might be effective antistaph agents.

The researchers tested their idea with nine such compounds. "Many of them have gone through clinical testing; they just don't happen to be as good as statins," Nizet said. "So they are languishing in clinical development."

That state of limbo might soon be over for one of them. Among the compounds the authors tested was BPH-652, which already has made it to Phase II trials as a cholesterol-lowering agent. They found that BPH-652 turned S. aureus bacteria white as a sheet, and with good reason: Nonpigmented S. aureus was roughly "4-fold less able to survive in freshly isolated human whole blood than were normally pigmented S. aureus," the authors reported.

That's not to say that high-school athletes should start stealing their elders' cholesterol medications for do-it-yourself staph treatment. Currently marketed cholesterol-lowering agents "work much further down in the pathway," Nizet said. "They would not be predicted to interfere with the pigment at all."

Nizet's lab is focused on targeting virulence factors to develop antibiotics. A virulence factor, Nizet explained, is "something that contributes to disease progression - in other words, anything that makes you sick." Bacterial toxins and communications systems such as quorum sensing are well-known bacterial virulence factors, but Nizet said factors that allow the bacteria to grow are "every bit as critical" to disease.

He sees several advantages to that strategy. For one, targeting staphyloxanthin synthesis also has effects very specific to S. aureus in the bloodstream, which is where it is a problem. The approach spares the bacterium in its normal habitat on the skin and in the nose, as well as what Nizet referred to as "other good citizen bacteria that live on and in us."

In general, targeting virulence factors has a different goal than the one pursued by currently marketed antibiotics. "You're not trying to kill the bacterium," Nizet explained. Instead, the goal is to weaken the bacterium enough for the immune system to finish it off.

Major pathogens, he said, "have the ability to overcome pretty much every part of our immune system" - from the complement system to innate immunity and antibodies. "If we can take away one of the components of their armor, then we can flip the odds dramatically back in favor of the patient."

Not killing the bacteria also means that there is less selective pressure on them to develop resistance. While it is theoretically possible that S. aureus strains could evolve changes in the synthesizing enzyme, Nizet pointed out that "the vast, vast majority of bacterial species we encounter in the environment have not evolved mechanisms to avoid immune clearance."