Two groups of synthetic biologists seeking to repurpose living microbes for human benefit have reported genetically modifying bacteria to detect cancer in mice and diabetes in humans.
Sangeeta Bhatia, a biomedical engineer at the Massachusetts Institute of Technology (MIT) in Cambridge, and her colleagues previously worked on cancer detection using metal nanoparticles. Unfortunately, Bhatia says, the signal was often too weak to serve as a clear indicator of disease. Bhatia’s team then realized that bacteria offered a potentially superior option. The researchers knew that microbes with a taste for tumor often penetrate the masses as they grow and replicate. So Bhatia’s group joined up with a team led by Jeff Hasty, a bioengineer at the University of California, San Diego, to reprogram bacteria that could be fed to mice and, in the presence of cancer, would produce a luminescent signal with a simple urine test.
They engineered the bacteria, Escherichia coli, to produce a naturally occurring enzyme called LacZ when they encountered a tumor, and then fed it to mice. Next, the researchers injected the mice with compounds that were precursors for light emitters. These were two-part molecules made up of a sugar linked to luciferin, a luminescent molecule. When bound together, the pair doesn’t emit light, but LacZ acts like a pair of scissors that cuts the two apart. So, in mice that had liver cancer populated by E. coli, the LacZ produced by the microbes released the luminescent compound, which was then excreted in the animals’ urine, turning those samples from yellow to red.
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