Like the web shooting from Spider-Man's wrist, ulcer-causing bacteria release a protein that snags its target in the gut. Then the microbe disrupts the ornate weave that holds stomach cells together, researchers have found. The work helps explain how the bacteria long known to cause ulcers and gastric cancer do their dirty work.
Two-thirds of the world's population is infected with Helicobacter pylori, which can live in the belly for 20 or 30 years before causing painful ulcers. They are also a common cause of gastric cancer. Researchers have known for some time that H. pylori reside near the top layer of cells lining the stomach, called the epithelium. Some strains of the bacteria set up camp at this destination and live peacefully without causing harm, while others slowly inject a protein called CagA into the epithelium. Infiltration of CagA somehow triggers disease, but the process is fuzzy.
To clarify the details, a team at Stanford University in California, led by microbiologists Manuel Amieva and Stanley Falkow, infected dog kidney cells--which mimic infection in humans--with H. pylori. They found that the bacteria gripped the sticky lattices holding the cells together. Examining cell slices under a microscope, the group saw that the bugs almost always stuck to a protein, common in the lattices, called ZO-1, which migrated close to where the bacteria were sitting.
Could CagA be the magnet that pulls ZO-1 toward the bacteria? Amieva's team checked out that prospect by creating an H. pylori strain that lacked the cagA gene. Those bacteria ended up scattered throughout the cells, and ZO-1 stayed in its original place in the lattice. Further studies revealed that CagA and ZO-1 team up to disrupt the epithelium's intricate meshwork, which they speculate could lead to ulcers and other diseases, the team reports in the 30 May issue of Science.
"This is definitely a provocative idea," says Karen Ottemann, a microbiologist and environmental toxicologist at the University of California, Santa Cruz. "The next step," she adds, "would be to show that some of these processes are important" in causing disease. Amieva thinks that is likely; lattice components are often out of whack in a number of cancers, he notes.