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Researchers Develop First Way To Immunize Against A Deadly Bacterium

ege of Wisconsin. The collaboration involved seven scientists from the two institutions, combining basic research in critical patient care and bacterial genetics to develop the antibody and demonstrate its ability to provide immunity against the Pseudomonas bacterium. First author on the paper is Teiji Sawa, MD, PhD, adjunct assistant professor of anesthesiology at UCSF.

The bacterium employs what is known as a type III secretory system to infect lung cells. A combination of at least 25 bacterial proteins work in concert to allow the microbe access to penetrate the outer surface of the host cell and inject toxins into it. The toxins are particularly difficult for the cell to defend against, Wiener-Kronish explained, because they wipe out the primary line of defense -- the macrophages which would normally engulf such invaders. The research team developed antibodies to five of the proteins in the bacterium's toxin delivery system and tested the ability of each to block the deadly process. One of the five, an antibody to the bacterium's PcrV antigen, prevented the invading microbe from destroying the lung cell macrophages. As a result, the cells could mount a defense against the bacteria and prevent delivery of the toxin. Most importantly, lung cells were protected, the researchers report.

The scientists do not yet know the precise role of the bacterial protein they have blocked. They know it is needed for successful delivery -- or translocation -- of the toxin from the bacterium to the lung tissue, and that it itself is not a toxin, they report.

Immunization could be useful not only against the Pseudomonas-induced pneumonia, but also against the devastating lung inflammations suffered by people with cystic fibrosis, says Wiener-Kronish. These same virulent bacteria cause the chronic inflammations of cystic fibrosis, and sufferers are never able to clear their lungs of the microbes. A systemic approach such as immunization may hold more promise than eff
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
30-Mar-1999


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