Project Lead(s): David McMillen
Many diseases are caused by ingesting bacteria from the environment.
Cholera, for example, is caused by ingesting Vibrio cholerae, usually from contaminated water supplies.
Many bacteria have viruses that prey on them, infecting the bacterial cells, using their cellular machinery to make many more copies of the virus, then bursting the cell to release the viruses back into the environment.
This project investigated the potential to use bacteriophages (a virus that infects and replicates within a bacterium), as a means of targeting disease-causing bacteria for destruction.
In principle, it may one day be possible to have engineered bacteria reside in the digestive tract of people at risk of exposure to a disease like cholera. The engineered cells would lie in wait until they sensed the presence of their target organism and, once detected, respond by triggering the release of bacteriophages to kill the incoming disease-causing organisms.
Because bacteria are self-replicating, they can be grown locally with minimal infrastructure.
The project used non-pathogenic bacteria E. coli to mimic the target bacteria cholera. (Cholera bacteria could not be used in the lab conditions because of safety concerns.)
The first prototype system was designed using E. coli and the lambda bacteriophage, which targets E. coli and is a well-studied bacteriophage system.
To gain experience with the actual biological components of cholera itself, the team also created a system able to sense the quorum-sensing molecules released by V. cholerae, and respond by producing a visible output signal.
To avoid working directly with V. cholerae, genes involved in production of the quorum sensing molecules were imported into E. coli cells, and these were used as a source of quorum sensing molecules.
Preliminary results suggest that the system will be able to successfully respond to V. cholerae’s signals, though more work is needed to couple this system to the other components.
The team also implemented the bacteriophage lambda prototype system in E. coli cells, and demonstrated that the cells could be triggered to burst on command, releasing viruses into their environment.
While this approach is promising, there is considerably more research required before any kind of clinical trial or commercial development can be undertaken.