Researchers have investigated out how the cancer-causing bacterium Helicobacter pylori attacks a cell’s energy infrastructure, sparking a series of events in the cell that ultimately lead it to self-destruct.
H. pylori are the only bacteria known to survive in the human stomach. Infection with the bacterium is associated with an increased risk of gastric cancer. “More than half the world’s population is currently infected with H. pylori,” says University of Illinois microbiology professor Steven Blanke. “And we’ve known for a long time that the host doesn’t respond appropriately to clear the infection from the stomach, allowing the bacterium to persist as a risk factor for cancer.”
The study shows how a bacterial toxin can disrupt a cell’s mitochondria to disable the cell and spur apoptosis. “One of the hallmarks of long-term infection with H. pylori is an increase in apoptotic cells,” Blanke says. “This may contribute to the development of cancer in several ways.” Apoptosis can damage the epithelial cells that line the stomach, he explains, “and chronic damage to any tissue is a risk factor for cancer.” An increase in apoptotic cells may also spur the hyper-proliferation of stem cells in an attempt to repair the damaged tissue, increasing the chance of mutations that can lead to cancer.
Previous studies have shown that VacA, a protein toxin produced by H. pylori, induces host cell death but the mechanism is unknown. The VacA protein was known to target the mitochondrion. While studying how a cell responds to infection, the researchers noticed that H. pylori induced mitochondrial fission. Instead of fusing and forming filamentous networks to respond to the cell’s energy needs, the mitochondria were breaking into smaller, unconnected organelles.
“Fusion and fission are two dynamic and opposing processes that must be balanced to regulate mitochondrial structure and function,” Blanke says. But infection with H. pylori (or with purified VacA toxin alone) was pushing the mitochondria toward fission.
The researchers found that VacA recruited a host protein, Drp1, to the mitochondria. Further experiments showed that Drp1-mediated fission of the mitochondrial networks was linked to activation of Bax, a cell-death-inducing factor. “The link between VacA action at the mitochondria and Bax-dependent cell death had previously been unknown,” Blanke says.
This study provides a link between a bacterial toxin-mediated disruption of mitochondrial dynamics and host cell death. It also opens an avenue of investigation of other diseases linked to impaired mitochondrial function. “Hundreds of human diseases and disorders are associated with mitochondrial dysfunction, ranging from cancers to degenerative diseases such as Alzheimer’s disease and Parkinson’s,” Blanke says. “As yet, no one has methodically investigated a potential link between bacterial infections and mitochondrial diseases, despite the fact that several dozen pathogenic bacteria and viruses are known to directly target mitochondria.”