February 14, 1997

Study reveals how bacteria ‘hides’ itself from immune system

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Dr. Martin Blaser is studying how a certain bacteria camouflages itself from the body's immune system.

Study reveals how bacteria 'hides' itself from immune system

Vanderbilt University Medical Center researchers studying the bacteria Campylobacter fetus have discovered a new mechanism by which the bacteria elude the immune system.

In a study published in the Proceedings of the National Academy of Sciences, VUMC investigators describe how the bacteria ‹ which is absorbed through the gastrointestinal tract and can cause meningitis and other infections ‹ camouflages itself by subtly rearranging its own gene makeup.

"We found that the bacteria wears a coat that makes it invisible to some of the body's defense mechanisms," said Dr. Martin J. Blaser, Addison B. Scoville professor of Medicine and professor of Medicine. "If you put it next to a white blood cell, the cell doesn't even know the bacteria is there. It just ignores it."

Blaser has been studying the bacteria for nearly 20 years to try to find ways to prevent its invasion into the body. Joel Dworkin, Ph.D., a fourth-year medical student at Vanderbilt University School of Medicine, co-authored the study, "Nested DNA inversion as a paradigm of programmed gene rearrangement." Dworkin's doctoral dissertation in the department of Microbiology and Immunology serves as the basis for much of this work, according to Blaser.

The body's immune system destroys invading bacterial cells by recognizing the proteins found on the surface of the cell. When the immune system detects a foreign protein, it mounts an attack against that cell and destroys it. The C. fetus bacteria, however, fools the immune system into thinking it is not even present.

"The bacteria does not just have one gene to form its coat protein, but a whole family of genes. We found that the bacteria is shuffling its own genes to keep ahead of the ability of the immune system to respond to foreign proteins," said Blaser.

The idea that cells shuffle their genes is not new. It has been known for some time that cells of the immune system splice their own genes in different ways to vary the antibody to express. The difference here is that this bacteria folds and cuts its DNA in a way that has not been seen in any other cell.

"Through a very neat system that Joel developed we have been able to carefully watch how the bacteria is shuffling its genes," said Blaser.

Knowing the mechanism behind this gene shuffling is not only valuable to working out strategies to defeat the bacteria but also for its application toward human biology.

Much of what is known about bacteria is also applicable to higher cells, including human cells.

Recently, Blaser has been contemplating a way to use the gene shuffling action of the bacteria to form new vaccines for prevention of tuberculosis, HIV, and respiratory infections.

"One of the ideas for applying this to HIV is that we could engineer an altered form of the bacteria so that it presents coats that we want, like the ones found on HIV," said Blaser.

The same process could be used for tuberculosis or respiratory infections. The plan would be to engineer different proteins into each of the different copies of the coat genes. Then, we could let the bacteria naturally shuffle the coats it was wearing.

"We could give it a whole wardrobe," said Blaser. "Rather then eluding the host's defenses it would express these foreign proteins that would permit the development of immune responses to prepare the body in case it ever came in contact with the real HIV virus or tuberculosis bacteria."