With this second post in a blog series covering the St. Louis Imaging Sciences Pathway (ISP) Retreat, we will see the research of a graduate student who works on a particularly bug-y form of cancer diagnosis and treatment. By bug-y, I don’t mean problematic; I mean the actual use of bacteria to track down and potentially even treat tumors in the human body.
Kelly Flentie is a PhD student in the microbiology program of Washington University in St. Louis. As a member of the university’s Molecular Imaging Center, Kelly is using bioluminescent imaging, a form of optical imaging, to study the interactions between bacteria and cancer cells. Bioluminescence is the production and emission of light by chemical reactions that occur inside of a living organism: think of the firefly, also called the lightning bug by insect-loving children in the summertime. A chemical reaction in the abdomen of the insect produces a light-emitting compound, a derivative of firefly luciferin, which literally makes the insect ‘glow in the dark’. These glow in the dark products can also be inserted into microscopic bacteria, giving rise to the use of microorganisms in diverse applications ranging from art to cancer diagnosis through bioluminescent imaging.
Kelly Flentie gave a talk at ISP on her astounding research, which consists of analyzing how glowing bacteria, specifically Salmonella enterica_, interact with cancereous tissues. The ‘glowing’ state of the bioluminescent bacteria allow researchers to image the bacteria through the skin and surface tissue layers of experimental animals, and thus analyze interactions between the bacteria and cancerous tissues in a non-invasivebench/2011/06/19/imaging-sciences-pathway manner. Such interactions include bacteria localization to malignant tumors when the bacteria are injected into tumor-bearing animals, and smaller-scale interactions between the bacteria and individual cancer cells. These interactions may change how the bacteria behave and which genes they express, enabling them to better colonize tumors, which have a different microenvironment than healthy tissues. The tumor microenvironment consists of both the tumor cells, neighboring normal cells, associated molecules and chemical conditions such as pH, that together make up the ‘ecosystem’ of the tumor.
Kelly’s studies join a trend of research findings that suggest bacteria like Salmonella may do far more than cause troubling infections in humans. These bacteria may be harnessed for not only cancer diagnosis through imaging, but also potentially for cancer treatment. Adaptations of Salmonella enterica to harsh evironments, including low pH conditions of the stomach, have given this strain its infamy in human infections such as gastroenteritis, which produces symptoms like that of food poisoning. But such adaptations may also be the basis of Salmonella enterica’s ability to preferentially populate tumors and cancerous lessions over healthy tissues in the body (image below).
Beyond using the preferential localization of glowing Salmonella bacteria to tumor sites for cancer diagnosis, researchers like Flentie are taking it a step further with plans to use special ‘bugs’ for cancer treatment. For example, genes that produced bacterial toxins like the Shiga toxin, which is currently adding to the deadliness of E.coli-1. outbreaks in Germany, may be engineered into tumor-hunting bioluminescent Salmonella bacteria. Perhaps these toxins could be put under the control of bacterial genes only expressed, i.e. their products only produced, under tumor microenvironment conditions. This and other means to transport drugs or anti-cancer compounds specially to tumors, and not to healthy tissues, would allow both tumor imaging and cancer treatment with the use of bacteria as targeted agents or live cancer ‘bullets’. Of course, clinical trials must ensure that cancer-hunting bacteria are completely safe for body-wide use in humans before they can be considered for widespread cancer diagnosis and treatment.
The use of glowing bacteria as cancer imaging or treatment agents is just one example of the new places that medical imaging, combined with other scientific disiplines, is taking us. Join me again soon as I discuss another Imaging Science Pathways Retreat discussion, this time on the subject of utilizing medical imaging to improve the design process of new drugs for the treatment of both common and rare human diseases!
Flentie KN, Qi M, Gammon ST, Razia Y, Lui F, Marpegan L, Manglik A, Piwnica-Worms D, & McKinney JS (2008). Stably integrated luxCDABE for assessment of Salmonella invasion kinetics. Molecular imaging, 7 (5), 222-33 PMID: 19123992
Leschner S, & Weiss S (2010). Salmonella-allies in the fight against cancer. Journal of molecular medicine (Berlin, Germany), 88 (8), 763-73 PMID: 20526574
1. another troublesome bacteria which can contaminate our green foodstuffs.