(492e) Programming Beneficial E. coli to Sense and Kill Vibrio cholerae, the Causative Agent of Cholera

WHO recognise the cholera disease, caused by the Vibrio cholerae bacteria, as potential worldwide threat to human health. Even though it is virtually eradicated in most of the developed countries of the world, it is still present in many African and Asian countries. It also can become an issue in places where the sanitary conditions worsen due to disasters like what happened in Haiti in 2010 after an earthquake. This situation is exacerbated by the fact that the current cholera treatment and prevention options are either limited or have low efficacy.

To address the problem, we have engineered a novel Escherichia coli strain, which is able to sense and kill V. cholerae in vitro. First, we have developed a genetic sensor device for E. coli to enable it to sense V. cholerae. We have done this by moving and refactoring the native quorum sensing system of V. cholerae in E. coli. This system is able to sense CAI-1 – chemical compound produced by V. cholerae and which accumulation in the medium signals presence of V. cholerae. This sensor was layered with CRISPRi based genetic inverter/amplifier to enable efficient production of signal molecule, which was GFP in this case. Next, this sensor has been layered with a killing device that made our E. coli to lyse and release a killing protein upon V. cholerae detection.

To the best of our knowledge, this is first example of such a genetic device. With further development, this strain could be turned into viable therapy/prevention method against cholera.