November 13, 2011 | 2
The discovery that stomach ulcers are caused by bacteria is quite recent and was proved fairly conclusively in 1984 when the Australian scientist Barry Marshall drank a petri-dish full of the bacteria Helicobacter pylori and five days later developed serious gastritis, which cleared after antibiotic treatment. As stomach ulcers are quite common, and can be a major source of duodenal ulcers and stomach cancer, the discovery that they could be treated by a course of antibiotics was of major medical importance.
Recently, researchers from the University of Illinois have discovered a bacterial toxin that plays a part in inducing cell death, or apoptosis, in the cells of the human host. The toxin is called VacA (for vacuolating cytotoxin A) and had been shown previously to induce cell death although the mechanism was not known.
Cell death plays an important part in the development of gastric cancers. The cells die by apoptosis, which is a program of cell death built into each cell in your body. Rather than attacking the cells of the stomach lining the Helicobacter pylori releases a chemical which causes them to quietly commit suicide. In order to induce this the VacA toxin targets the mitochondria; the parts of the cell that are dedicated to producing energy.
Once the VacA gets into the cell of the stomach lining it heads straight for the mitochondria. In order to produce energy for the cell, mitochondria need to maintain a difference in electron gradient between their outer and inner membrane (you can just about see the double membrane surrounding the cells in the image above). The VacA activates a system which makes the outer membrane permeable, all the ions diffuse out of the inter-membrane space, the electron gradient disappears and the mitochondria essentially stop working.
As well as screwing around with the mitochondrial function, the VacA also disrupts the mitochondrial structure. While the image above is a great demonstration of what dead mitochondria look like, in a living cell mitrochondria are fairly plastic. They spread out, blobaround, divide up and form an interlinked network within the cell. The VacA stops all that. After introducing the VacA the nice interlinked mitochondrial network breaks up, leaving just isolated single mitochondrion blobs.
Having healthy mitochondria is vital for animal cells. As multicellular creatures exist within a closely controlled cellular environment, the minute the mitochondria start to go weird the most common response for the cell is to kill itself through apoptosis. By disrupting this important part of the cellular machinery, the Helicobacter pylori can cause the death of stomach cells in a small specified area, which can lead to peptic ulcers and, in severe cases, gastric cancer.
Picture credit image one
Picture credit image two (there are some wonderful intracellular images here, all in the public domain!)
University of Illinois press release.
Jain P, Luo ZQ, & Blanke SR (2011). Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death. Proceedings of the National Academy of Sciences of the United States of America, 108 (38), 16032-7 PMID: 21903925