Recently, methicillin-resistant Staphylococcus aureus, or MRSA, has been much on the public's mind. A paper in the Journal of the American Medical Association reporting that MRSA now causes more deaths than HIV, combined with news reports of previously healthy schoolchildren dying of community-acquired MRSA infections, has led to a full-blown public-health panic in parts of the country.

It is worth pointing out that, although MRSA and other drug-resistant bacteria are undeniably a growing concern, the data reported in JAMA have as much - or more - to do with medical triumphs against HIV as with treatment failures of MRSA, and that there are effective drugs available against methicillin-resistant staph strains.

Still, MRSA is, at almost 19,000 deaths annually, a serious problem. And although most deaths are due to hospital-acquired MRSA, it is the community-acquired MRSA, virtually unknown until fairly recently, that is actually more virulent, sometimes killing previously healthy individuals. In a further worrying development, such strains appear to be making their way back into hospitals, where virulence and drug resistance could combine to give the medical community a bug with the worst of both worlds.

Research published in the Nov. 11, 2007, early online version of Nature Medicine reported on the mechanisms that community-associated MRSA uses to evade the immune system and cause severe disease. Actually, "evade" may be the wrong word. Community-associated MRSA is nasty because it has found a way to attract, activate and destroy leukocytes, "their major enemy in the body after infection," senior author Michael Otto told BioWorld Today.

A few years ago, most researchers thought the virulence mechanisms of CA-MRSA were clear. Because a lytic toxin by the name of Pantone-Valentin leukocidin or PVL is present in community-associated but not hospital-associated strains of MRSA, "many people believed . . . that PVL is what determines virulence," said Otto, who is a senior investigator at the National Institute of Allergy and Infectious Diseases' Rocky Mountain Laboratory.

But in 2006, Otto and his team showed that CA-MRSA strains were as virulent without their PVL genes as with them, meaning that the culprit must be another protein.

In their Nature Medicine paper, Otto's group, along with colleagues at the University of Tuebingen and the University of Washington, described studying another family of proteins, phenol-soluble modulins, or PSM peptides, which causes an inflammatory response when secreted by other Staphylococcus strains. Findings revealed that those peptides are "expressed at a high rate in community-associated strains" compared to hospital-associated strains, Otto said.

By knocking out PSM genes from CA-MRSA strains, the scientists pinpointed the PSM-alpha gene cluster as having an essential role in CA-MRSA virulence and, ultimately, disease severity. Adding PSM genes back via plasmids restored virulence to bacterial strains. PSM-alpha appears to work by first attracting white leukocytes and then destroying those cells when they heed the call.

As for the therapeutic implications of his discoveries, Otto said that there is a school of thought that advocates targeting virulence factors for antibiotics. But, he added, "I disagree with that [approach]."

The reason, he said, is that a lack of virulence factor does not kill the bacteria; therefore, targeting it does not get rid of the actual infection even though it will make the patient feel better. For that reason, Otto believes virulence factors "might be interesting to target in combination therapy with conventional antibiotics."

Aurograb, which was developed by NeuTec Pharma plc of Manchester, England, and is now owned by Novartis AG, of Basel, Switzerland, is based on targeting virulence factors, Otto said. But aurograb is being tested as an adjunct therapy to vancomycin, and "is not supposed to be a stand-alone" treatment.