PATHOGENS IN MIGRATION
Following E.coli's journey through the body may help discover ways to stop it

Timothy Morgan, assistant professor of pathology at the LSU School of Veterinary Medicine, is researching the body’s response to Escherichia coli O157:H7.  This pathogen, also known as enterohemorrhagic E. coli or EHEC, is responsible for some 73,000 cases of food borne illness in the United States each year.  Around 15% of those infected (mostly children and elderly persons) will develop a condition called hemolytic uremic syndrome, or HUS.  HUS is fatal in up to 5% of cases and is the leading cause of acute kidney failure in children of industrialized countries around the world.

Timothy Morgan, DVM

HUS occurs when toxins produced by EHEC move from the intestinal lumen into systemic circulation. These compounds—called Shiga toxins because of their similarity to those produced by Shigella, the bacterium that causes dysentery—are potent chemicals and lethal to endothelial cells that line the insides of blood vessels in the kidneys and brain. Death of endothelial cells leads to the formation of small but damaging blood clots in these organs, producing HUS.

Morgan hopes to learn how this toxin migrates through the body. “What we’re looking at,” he said, “is the mechanism by which Shiga toxin moves from the intestine to the systemic circulation or blood stream.”

Morgan’s work targets how an infected individual’s own immune response may facilitate the toxin’s ability to escape the intestine:  “Our hypothesis is that the host inflammatory response to E. coli O157:H7 alters the mucosal barrier in the intestine in such a way that Shiga toxin is more readily able to move into the blood stream.”

Morgan is specifically interested in the role of the neutrophil, a type of white blood cell that fights acute infections, in changes in mucosal permeability with respect to Shiga toxin. Neutrophils attack and destroy invading organisms; however, in doing so they may also damage the surrounding tissue, in this case intestinal epithelium cells that normally function to prevent the absorption of toxins.  When neutrophils move from the blood into the intestine to attack E. coli, they must migrate between these epithelial cells.  Both this migration and the neutrophils’ collateral cell damage can affect intestinal permeability.

  “It’s interesting that our own defense mechanisms may be a contributing factor in this disease,” said Dr. Morgan.  “If the host inflammatory response is contributing to the absorption of Shiga toxin in this disease, we may be able to reduce or prevent Shiga toxin absorption by suppressing the host inflammatory response.”

-by Kathleen Harrington

from Summer 2007 Issue