The RAP on Staph Infections

The dangerous pathogen Staphylococcus aureus causes infections ranging from skin abscesses to toxic shock syndrome. Roughly one-third of the strains currently isolated from patients who acquire S. aureus infections while hospitalized are resistant to all antibiotics but one, vancomycin--and now resistance to that antibiotic has begun cropping up. But new research suggests an approach to combating S. aureus that may sidestep the organism's ability to develop resistance.

In tomorrow's Science, researchers report that they can decresase the incidence and severity of S. aureus infections in mice by blocking the ativity of a protein called RAP, which controls the production of toxins and other proteins that make the bacterium pathogenic. The work suggests that disabling RAP--perhaps by vaccinating people with the protein so that the immune system takes it out of commission, or by developing drugs that prevent it from doing its job--might keep the microbe from spreading within the body before the patient's immune system flushes it out. Such drugs wouldn't kill the organism directly, and in the absence of such selective pressures, resistant strains might be less likely to develop.

Naomi Balaban, an infectious-disease researcher at the University of California, Davis, Medical Center in Sacramento discovered RAP and its role a few years ago. Her previous work suggested that as S. aureus multiplies, it secretes RAP. When the protein reaches a critical concentration, it sends a signal that turns on genes for producing toxins. That hinted, says Balaban, that the protein might make a good target for prevention strategies. She and her colleagues inoculated mice with RAP purified from S. aureus cultures. The vaccinated animals developed antibodies to RAP, and when the researchers injected S. aureus under the animals' skins, only 28% developed skin lesions, compared to 70% of controls.

Because it takes weeks to mount an immune response, such a vaccine would benefit those whose risk could be anticipated, such as diabetics and kidney dialysis and surgery patients. But "this opens a whole new strategy for treating or preventing one of the most serious hospital infections we contend with," says Julie Gerberding, an infectious-disease specialist at the University of California, San Francisco. "Methods that prevent disease without selecting for drug resistance could really help us--and we're going to need help soon."

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