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Wednesday, September 9, 2009

Could Salmonella Bacteria Kill Tumors?
ScienceDaily (Sep. 8, 2009) — Salmonella is regarded as a bad guy. Hardly a summer passes without reports of severe salmonella infections via raw egg dishes or chicken. But salmonella may not only harm us -- in the future, it may even help to defend us against cancer. Researchers may soon have a way to make the bacteria migrate into solid tumors in order to make it easier to destroy them. Furthermore, in laboratory mice, the bacteria independently find their way into metastases, where they can also aid clearance of the cancer.


In the scientific journal PLoS One, Sara Bartels and Siegfried Weiss of the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany now show how the bacteria migrate into tumors. A messenger substance from the immune system is the door opener: It makes blood vessels in the cancerous tissue permeable; enabling the bacteria to conquer and destroy the tumor. Simultaneously, blood streams from the vessels into the cancerous tissue, a so-called necrosis develops – and the tumor dies. “This influx of blood was the starting point for our investigations,” says Siegfried Weiss, Head of the Molecular Immunology group at the HZI.

“There is an immunological messenger present during bacterial elicited inflammation that causes this kind of reaction. We searched for it – and found it.” This messenger is named after its role in the immune system: tumor necrosis factor, TNF-alpha for short. Immune cells produce TNF-alpha when recognising salmonella, thus alarming other immune cells. This inflammatory reaction leads to an increased blood vessels permeability an action that also occurs in a tumor: TNF-alpha has an easy task here because the blood vessels in cancer differ fundamentally from healthy arteries or veins. They are irregularly built, porous, partially with dead ends. A small amount of TNF-alpha is subsequently enough to dissolve the walls of the blood vessels in the tumor and allow the blood to stream into the cancerous tissue.

The scientists hope to be able to modify salmonella so they can be used in tumor therapy. The aim is for the bacteria to migrate specifically into tumors and cause them to die. The attractiveness of this way of destroying tumors is the lifestyle of salmonella. They can live almost everywhere, including tissues, which are badly supplied with blood and thus have hardly any oxygen supply. And it is precisely these areas that are scarcely reachable in a cancerous ulcer using common cancer therapies: chemotherapeutics cannot be transported to an area where there is no blood flow. And even radiation therapy requires oxygen for its reactions in the tissue.

The phenomenon of bacteria attacking tumors has been known to scientists for a long time. However, a cancer therapy with potential pathogens has been unthinkable before now. The risk of the patient dying due to an infection was too high. “We have obtained an important indication of how bacteria migrate into tumors. We can now try to manipulate these bacteria to use them in cancer therapy without causing deadly infections,” says Sara Bartels.

Bacteria Take On Completely New Flat Shape To Fit Through Nanoslits
ScienceDaily (Sep. 9, 2009) — It appears that bacteria can squeeze through practically anything. In extremely small nanoslits they take on a completely new flat shape. Even in this squashed form they continue to grow and divide at normal speeds. This has been demonstrated by research carried out at TU Delft's Kavli Institute of Nanoscience. The results will be appearing this week in the online edition of the scientific journal Proceedings of the National Academy of Sciences (PNAS) and as the cover article in the September 1 print issue of PNAS.


Using nanofabrication, Delft scientists made minuscule channels, measuring a micrometer or less in width and 50 micrometer in length, on a silicon chip between tiny chambers containing bacteria. Subsequently they studied the behaviour of Escherichia. coli and Bacillus. subtilis bacteria in this artificial environment. The bacteria were genetically modified so that they were fluorescent and could easily be followed using a special microscope.

Squashed flat

Under normal circumstances these bacteria swim and this research showed that they retain this motility in surprisingly narrow channels. They swam just as actively as usual even in channels that were only 30 percent wider than their own diameter (of about 1 micrometer). In even narrower submicron channels the bacteria stopped swimming, and an unexpected effect took place: The bacteria were able to make their way through ultra-narrow passageways in another manner, that is by growing and dividing. The researchers found that this way, E. coli bacteria could squeeze through narrow slits that were only half their own diameter in width.

Post-doctoral researcher, Jaan Männik said, "This took us totally by surprise. The bacteria become completely flattened. They have all sorts of peculiar shapes both in the channels and when they finally come out at the other side. What is really remarkable, however, is that in the channels, and therefore under extreme confinement, they continue to grow and divide at normal speeds. Apparently their shape is not a determining factor for these activities."