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Uncovered: Bacterial proteins that hide from immune system
Scripps Howard News Service


January 13, 2006
Friday AM

Researchers have unmasked a gang of proteins that some of the world's nastiest germs use to hijack our cells and hide from attacks by the immune system.

The 24-member family of bacterial proteins, called effector proteins, is described by University of California-San Diego scientists in a report published Friday in the journal Cell.

By learning how these proteins are able to hijack the body's communications network to block responses to salmonella, shigella and pathogenic E. coli, the researchers believe they might have opened a door to new types of treatments against bacterial diseases.


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"While discovery of this family of effector proteins was surprising, finding the mechanisms that these proteins use to attack human cells was even more exciting," said Neal Alto, a postdoctoral fellow at UCSD and lead author of the study.

When disease-causing bacteria are ingested, as they are in food-poisoning diseases like E. coli or salmonella, the bacteria use a syringe-like system to inject the human or animal host with the proteins through the normally tight defensive cell lining of the gut. Once inside a host cell, the protein hijackers re-direct the cell's communication network, and allow the bacteria to take up nutrients and shut down the immune response.

"These proteins mimic known host proteins in the cell in a very interesting way," said Jack Dixon, scientific-affairs dean and professor of cellular and molecular medicine at UCSD's school of medicine, and senior author of the study.

"They are functional mimics that work in the same way as proteins of the host cell, but they don't look anything like the host proteins. In a sense, they take over the host cell's identity like a bad actor," Dixon said.

The scientists used molecular "fingerprinting" to identify the family of proteins. Using the fingerprints and computer-aided searches, they discovered a number of proteins having the same molecular pattern.

All of these were used by infectious bacteria. Then, the researchers determined that other bacterial proteins used a common strategy to hijack host cells' signaling pathway so that they can't call for help from immune system cells.

"These bacteria proteins are the bad guys that make you sick," by breaking through the barrier of cells lining the intestine and colon, Alto said. "Instead of curing the illness by giving a patient antibiotics, it might be possible to target these effectors, turning their virulent actions into something benign."

New treatments blocking the proteins' actions could be particularly helpful in combating illnesses like dysentery and other bacterial diseases in less developed nations where antibiotics are costly and hard to administer.

The findings could also help fight disease in people suffering from suppressed immune systems and HIV/AIDS.

The research team came from several disciplines at UCSD and the University of Toronto.


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