Two studies demonstrate how genetically engineered bacteria can be used to diagnose cancer and diabetes
Bacteria are an increasingly popular research focus for a range of disease states. But as well as causing diseases, bacteria could help to identify them – two studies published in Science Translational Medicine have demonstrated the diagnostic uses of genetically engineered bacteria in the detection of cancer and diabetes. In one study, US researchers engineered Escherichia coli Nissle 1917, a strain often used in probiotic products, to produce the enzyme LacZ when in the presence of tumors. When the E. coli strain was fed to mice, it was shown that the bacteria were able to colonize tumors in the liver. Next, the mice were injected with LuGal, a conjugate of luciferin and galactose, which can be converted to luciferin by LacZ. Luciferin can then be detected in the urine using a simple assay; with as little as 1 microliter of urine, the test was able to detect the presence of the bioluminescent luciferin (1). Using this method, the team were able to detect metastatic tumors within 24 hours of introducing the bacterial strain to the mice.
Meanwhile at the University of Montpellier, France, bacteria were also put to work – this time, to detect elevated glucose levels in the urine, a key sign of diabetes. The team incorporated a genetic “switch” into E. coli which caused the bacteria to produce large amounts of fluorescent protein when exposed to high concentrations of glucose. Unlike the previous study, the bacteria were not introduced to the body, but instead simply added to human urine samples. The approach doesn’t significantly improve on current glucose detection methods, but the developers are hopeful that as bacterial diagnostic methods improve, they will have a promising range of applications; engineered bacteria could potentially be developed to detect a range of clinically relevant biomarkers. “Our work is presently focused on the engineering of artificial genetic systems that can be modified on demand to detect different molecular disease markers,” says first author of the associated paper (2), Alexis Courbet. However, the use of bacteria as diagnostic tools still has challenges to overcome: the time to results is currently too long for urgent or emergency testing, and engineering bacteria that can respond to the right biomarkers is no simple task. The use of live, engineered bacteria in the lab could also raise safety issues. Certainly, any proposed methods will need further validation before seeing clinical use.
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References
- T Danino, et al., “Programmable probiotics for detection of cancer in urine”, Sci Transl Med, 7, 289ra84 (2015). PMID: 26019220. A Courbet, et al., “Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates”, Sci Transl Med, 7, 289ra83 (2015). PMID: 26019219.
