There was a time not long ago that methicillin resistant Staphylococcus aureus, or MRSA, was primarily a problem in hospitals, which are their best breeding grounds. Now, however, MRSA infections, like those caused by other multidrug-resistant bacteria, continue to be on the rise. They also increasingly are venturing into the wild, and community-acquired MRSA is now a regular occurrence:

A paper in the Jan. 18, 2007, issue of Sciencexpress, the early online version of Science, reports on the toxins that make certain versions of community-acquired MRSA, deadly.

"Every year clinicians in large cities see more patients with this type of infection," senior author Gabriela Bowden told BioWorld Today.

MRSA most commonly causes skin infections, but more serious cases can cause pneumonia, and when they do, the pneumonia can in turn cause massive tissue necrosis. Bowden said that reports vary, but community-acquired MRSA causes necrotizing pneumonia in 5 percent to 10 percent of all cases.

Bowden, a research assistant professor at Texas A&M University in Houston, and her colleagues at Texas A&M and the University of Lyon, Inserm, and the H pital Edouard Herriot of Lyon, France, wanted to test the role of the protein Panton Valentine Leukocidin, or PVL in necrotizing pneumonia. While different staph strains use different toxins for their dirty work, the most common strains in the U.S. and Europe express PVL, which forms a pore in neutrophils and macrophages and essentially causes them to lyse, or burst.

The researchers first created otherwise genetically identical strains of staph bacteria either with or without the PVL protein, and used them to infect mice. Mice infected with PVL-containing staph strains showed much more serious symptoms of pneumonia than their peers who were infected with non-PVL staph. In particular, their lungs showed strong inflammation as well as signs of necrosis and hemorrhage.

When Bowden and her team supplemented the PVL-negative staph strains with a separate plasmid encoding PVL, however, their lungs sustained massive damage, and in several experiments, anywhere from 35 percent to 80 percent of them died within 24 hours of being infected.

Protein expression experiments revealed that PVL-containing strain show stronger expression of two other proteins, which go by the poetic names SdrD and protein A, or spa. And the expression of spa, in particular, has a nasty synergy with PVL: Spa is a proinflammatory factor, and the combination of PVL, which causes cells to burst, and the inflammatory protein spa causes what Bowden and her team termed "a vicious cycle of cell recruitment, lysis and release of inflammatory mediators."

When they tested PVL and spa separately and together for the damage the two proteins did, the scientists found that while PVL in itself was sufficient to give mice pneumonia, it was the combination of PVL and spa that caused high fatality rates.

Next, Bowden's group wants to test whether targeting PVL can help fight necrotizing pneumonia. "We will try to test if antibodies specific to PVL can block the toxin and help clear the infection," she said.

Such antibodies essentially would buy time for those infected with community-acquired MRSA. "Sometimes, it's so fast that there's no time for antibiotics to work," she said.