Researchers find protein to combat dangerous staph bacteria In this story: Protein controls toxin production RAP 'disarms' the bacterium No proof yet that vaccine would work Related Stories and Sites April 16, 1998 Web posted at: 8:23 p.m. EDT (0023 GMT) WASHINGTON (CNN) -- Researchers have discovered a protein that may outwit one of the world's toughest bacteria and provide a vaccine that would avoid the dangerous drug resistance that is producing so-called "superbugs." Naomi Balaban, who led a research team at the University of California at Davis, said the hope is that the new approach would provide an alternative to antibiotics. The work is still in its early stages, but 72 percent of the mice vaccinated with a protein called RAP were protected against staph infections. Writing in the journal Science, Balaban said she found a way to stop staph bacteria from producing the toxins that make it dangerous. "Unlike antibiotics," said Balaban, an infectious disease specialist, "it does not kill the bacteria, so there is no pressure on the bacteria to mutate. "It's all by peaceful terms for the bacteria, so maybe it won't resist it as much," she said. Staphylococcus aureus -- staph for short -- is the most common cause of infection in the United States. It causes infections ranging from harmless pimples to toxic shock syndrome and pneumonia. It is a particular threat in hospitals, infecting up to 500,000 hospitalized Americans every year. It is usually easy to treat with antibiotics, but drug-resistant forms have evolved, creating so-called "superbugs." Most frightening is a strain that resists vancomycin, a powerful antibiotic that is considered the last line of defense against bacteria. Only three cases have been reported, but experts predict there will be more. Protein controls toxin production "We desperately ... need innovative strategies to deal with staph infections," said Dr. Stephen Heyse of the National Institutes of Health, which awarded a biotechnology company $100,000 last month to begin work on the vaccine. "This approach was quite novel and interesting." The discovery "shows a lot of promise," said Harvard University microbiologist Jean Lee. Balaban said the bacteria doesn't necessarily cause disease because it enters the body, "but because of the toxins it produces." Fighting each separate toxin would be unwieldy and time-consuming, so Balaban looked for a protein that controls all toxin production, and she found it. She called the protein RAP, for "RNAIII activating protein." When staph bacteria enter the body, they secrete RAP until enough is produced to set off a chain reaction that creates staph toxins. If the bacteria cannot produce enough RAP, the germs are harmless, Balaban said. Her idea was to use RAP as a vaccine, spurring the immune system to produce antibodies that would recognize the protein once staph bacteria began churning it out and neutralize it. That would disarm staph before it causes serious infection. And because a RAP vaccine wouldn't kill the actual bacteria, as antibiotics do, it wouldn't spur the bugs to mutate into drug-resistant forms that now threaten to become untreatable. RAP 'disarms' the bacterium "The bacterium doesn't realize it's being jeopardized," she says. "No RAP, no toxins, no disease." Scientists are furiously searching for new means to combat bacteria to replace antibiotics. They have tried vaccines that would prime the body to attack bacteria directly, but those attempts haven't worked well. But rather than attacking the staph germs and trying to kill them, the RAP protein disarms them instead. Balaban vaccinated mice with RAP purified from a strain of staph that causes skin lesions, and then exposed the mice to the staph germs. Mice who got injections of staph along with a second protein, a peptide called RIP (for "RNAIII inhibiting peptide"), were much less likely to develop infections. All of the unvaccinated "control" mice became infected, but only 28 percent of the vaccinated mice did -- and they had 76 percent smaller skin lesions than the unvaccinated mice. Three percent of the vaccinated mice died from their infection as opposed to 25 percent of the untreated mice. No proof yet that vaccine would work Balaban said RIP could be developed as a coating to put on catheters, a notorious cause of staph infections, or tampons, which can cause toxic shock syndrome. Milk pumping machines that can produce mastitis, an udder infection in cows, are another candidate for RIP coatings. Her findings don't prove that a RAP vaccine would work, warned Harvard's Lee. A skin infection is the easiest staph to overcome, so the real challenge is trying RAP against more life-threatening systemic staph infections, something Balaban says she plans to do. Even if a vaccine eventually worked, at-risk people like the frequently hospitalized or health care workers would have to get it before they got the infection. So Balaban is also looking for a drug that would disarm staph once someone is sick. Her candidate is a RAP relative. The biotech company Panorama Research Inc., in Mountain View, California, is helping to develop Balaban's research, but experiments on humans are several years away. Balaban says her approach mimics how nature protects against staph. She recently tested cows and found that 80 percent of the animals who have never been sickened by staph naturally harbor antibodies that neutralize RAP -- while sick cows didn't have that immune response. "This approach may not necessarily replace antibiotics," she said. But "it seems like anti-RAP antibodies are really important for protection." Besides preventing the evolution of drug-resistant staph, Balaban said, the new approach has another advantage. Antibiotics can kill off the useful bacteria in the body, such as those that help digestion. The result can be yeast infections. Treating an infection without killing bacteria would help maintain the healthy balance of microorganisms in the body. The Associated Press and Reuters contributed to this report.