Salmonella bacteria
Editor’s note: Yesterday we wrote about how microbiome bacteria may be protecting cancer cells, but today we wanted to write about how microbiome bacteria can be engineered to kill cancer cells. Enjoy.
In 2003 a group at the Harvard Medical School discovered that nonpathogenic Salmonella (a microbiome bacterium) that was injected into mice would preferentially accumulate in the tumors of those mice, sometimes by a factor of 10,000. Soon after, the researchers tried to apply these findings to target and destroy cancer cells. They began incorporating cancer-fighting proteins into the Salmonella with the hopes that the bacteria would accumulate in tumors and destroy them. This was effective in killing the cancer, but the Salmonella was not specific enough to tumors, and the low levels that existed in healthy tissues still expressed anticancer proteins which killed the healthy tissues. Recently though, this problem may have been solved. One of the original scientists from Harvard Med, who now has his own group at UMass Amherst, developed a clever way to only trigger the anticancer proteins in Salmonella that are on cancer cells. His group published their results in the Proceedings of the National Academy of Sciences on Wednesday.
The scientists incorporated a genetic switch in the Salmonella which would only trigger the production of anticancer proteins around cancer cells. In order to do this they took advantage of the fact that the Salmonella accumulates to higher concentrations on cancer cells. Many bacteria have proteins called quorum sensing proteins. They are used by individuals and communities to sense what is around them, and to communicate with other bacteria. Some of these quorum sensing proteins are only activated by their genes when there are enough other bacteria around them. The scientists from UMass utilized this fact to incorporate a quorum sensing gene into Salmonella that would only activate a specific protein when it was around a high concentration of other Salmonella (e.g. in cancer cells).
The scientists incorporated this quorum sensing gene into Salmonella so that, when triggered, it would express a fluorescent protein (which could be easily visualized). They then injected these Salmonella into mice with various tumors. They discovered, as they had hoped, that the fluorescing protein was predominantly expressed in cancer cells, and at very low levels elsewhere. Moreover, the fluorescent protein was expressed for at least 24 days, and it did not appear to be expressed in other tissues (such as the liver) at all.
These experiments provide a partial proof of concept for a unique bacterial treatment to cancer. The next step is to test anticancer proteins instead of fluorescing proteins, but the results using the fluorescing proteins are promising. The scientists mentioned that the Salmonella used is non-pathogenic and can be eliminated from the body through natural processes. This is a rather innovative potential cancer treatment, and we are excited to see what its future holds.