In spite of our long and painful relationship with Campylobacter jejuni, we are just starting to answer basic questions about the bug that is the leading cause of bacterial food-borne illness in the United States, and one of the most common causes of diarrhea worldwide. The Centers for Disease Control estimate that "campylobacterioisis" strikes 2.4 million Americans a year.
While most sufferers recover after a few unpleasant days, it can be life threatening to those with compromised immune systems. A rare but serious complication of C. jejuni infection is the triggering of the autoimmune disorder, Guillain-Barrι paralysis.
Yale researchers now have some answers to one of the most basic puzzles surrounding C. jejuni infections. How could such a large bacteria gain access to human intestinal epithelial cells that do not normally take up particles of such size" And once inside, how does C. jejuni disappear off the conventional endocytic road map"
Robert Watson and Jorge Galan of Yale University School of Medicine report that C. jejuni apparently rolls in on the cell's regular endocytic pathway but quickly exits, heading off-road for its own network of intracellular hideouts. These C. jejuni-filled vacuoles make their own way toward the nucleus, taking up strategic positions near the cell's transportation hub, the Golgi apparatus.
Previous studies showing C. jejuni gaining intracellular access to intestinal epithelial cells despite its large size suggested to Watson and Galan that the bug had evolved a special mechanism to induce its uptake into these nonphagocytic cells and establish its own intracellular niche. Watson and Galan set out to follow C. jejuni down the host cell's endocytic pathway. Much of the cell's incoming traffic is usually routed to compartments called lysosomes, where an acidic brew of hydrolase enzymes chews it up. By monitoring endosomal marker proteins, the researchers could watch as C. jejuni infected a host cell, and was briefly cloaked in the early endosomal marker EEA-1, and then the late endosomal marker Lamp-1. Was C. jejuni trafficking to conventional lysosomes after all" To check, the researchers fed traceable dyes to infected cells. Taken up into the endocytic pathway, the fluorescent dyes co-localized with control bacteria known to traffic to lysosomes, yet surprisingly the dyes were unable to enter vacuoles containing C. jejuni. The bug had left the conventional endocytic pathway.
Watson and Galan also investigated the roles of two Rab GTPases, proteins involved in the maturation of endosomal compartments. These and other experiments provided additional evidence that C. jejuni leaves the normal endocytic pathway early and that the segregated C. jejuni vacuoles move to a perinuclear location where they become closely associated with the Golgi apparatus. The resulting full-scale invasion of millions of cells lining the gut can't be ignored.
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