New study is a step closer to the synthetic microbiome, inbuilt disease sensing and treatment.

More than 1,000 species of bacteria have been identified in the human gut, these symbiotic bacteria are known as the microbiome which is intricately involved with establishing and maintaining the health of the host.  Engineering of gut microbes aims to add new functions and expand the scope of control over the gut microbiome. To develop these systems which can perform increasingly complex tasks in the gut, it is necessary to harness the ability of the bacteria to communicate in the gut environment.  However, little is known about how all these different strains of bacteria communicate with each other, and whether it is possible to develop the types of signaling pathways to enable the flow of information between them.  Now, a study led by researchers at Harvard University engineers a genetic signal-transmission system in which a molecular signal sent by Salmonella Typhimurium bacteria in response to an environmental cue can be received and recorded by E. coli in the gut of a mouse.  The team states that their data brings the global medical community a step closer to developing a synthetic microbiome composed of bacteria that are programmed to perform specific functions. The study is published in the journal ACS Synthetic Biology.

Previous studies show that bacteria are routinely genetically engineered, with the hope of tweaking the genes of these intestinal interlopers so that they can do more than just help digest food.  The main desire is that a synthetic microbiome can be developed to record information about the state of the gut in real-time, and report the presence of disease or suspicious activity.  However, bacterial quorum sensing, a bacterial information transfer system, has not been identified in normal healthy mammalian gut.  The current study repurposes a type of quorum sensing known as acyl-homoserine lactone (acyl-HSL) using genetic engineering to enable information transfer between to different bacterial species.

The current study introduces quorum sensing via two new genetic circuits, a signaler circuit and a responder circuit, into different colonies of a strain of E. coli bacteria. Results show that the signaler circuit contains a single copy of a gene called luxI that is turned on by the molecule anhydrotetracycline (ATC) and produces a quorum-sensing signaling molecule. Data findings show that the responder circuit is structured such that when the signaling molecule binds to it, a gene called cro is activated to produce the protein Cro, which then turns on a memory element within the responder circuit; the memory element expresses LacZ which causes the bacterium to turn blue if plated on a special agar, thus producing visual confirmation that the signal molecule has been received.

Results show that this system works in vitro in both E. coli and S. Typhimurium bacteria, with the responder bacteria turning blue when ATC was added to the signaler bacteria. Data findings show in vivo that all mice display signs of signal transmission, confirming that the engineered circuits allowed communication between different species of bacteria in the complex environment of the mammalian gut.

The team surmise that they repurposed quorum sensing to develop an information transfer system between native gut E. coli and attenuated S. Typhimurium in the murine gut.  For the future, the researchers aim to develop a synthetic microbiome with engineered bacteria species in the human gut, each of which has a specialized function, such as detecting and curing disease, creating beneficial molecules, improving digestion, and communication between engineered bacterial species to ensure that they are all balanced for optimal human health.

Source: Wyss Institute for Biologically Inspired Engineering 




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