Researchers at the University of Kentucky report today the discovery a novel attack route used by one of the plague bacterium's killer toxins. Their work with Yersinia pestis, the bacterium which causes the plague, is published in the Nov. 28 issue of Molecular Microbiology. The study provides new clues about how a toxic protein called YopM, originally discovered at UK, targets and attacks the cell's nucleus. Only two other pathogenic bacterial proteins are known to enter the nucleus of cells.
"This finding raises the intriguing possibility that YopM may contribute to the development of disease by altering human gene expression," said Susan Straley, Ph.D., professor of microbiology and immunology, UK College of Medicine, and director of the research team for the project. "We believe that further study of the mode of action of this protein in host cells will provide insight into bacterial causes of disease and cell biology."
Yersinia invades an organism and attaches itself to cell surfaces. YopM is one of six toxins called Yops that Yersinia injects directly into the cell. Yops act by scrambling the functions necessary for humans to mount a defense against the bacteria.
Little is known about how these mysterious toxins function to destroy the immune response, but researchers believe Yops target phagocytic cells, the body's first line of defense against invaders. The bacterial killing response of the phagocytic cells is paralyzed, and the cells are rendered incapable of sending messages to other cells to begin an immune response to the pathogen.
UK researchers propose that YopM uses complex interactions to reach and
pass through the controlled gates of the nucleus. They believe YopM binds to
the exterior of acidic compartments, called endosomal vesicles, and moves as new
vesicles arise. YopM may act to prevent enter the nucleus by itself or it may
become associated with a protein. Once the nucleus is invaded, YopM
Contact: Vikki Franklin
University of Kentucky Medical Center