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

More than one thousand species of bacteria have been identified in the human gut, dubbed the microbiome, with these symbiotic bacteria intricately involved in establishing and maintaining the health of the host.  The engineering of gut microbes aims to add new functions and expand the scope of control over the gut microbiome. To develop synthetic systems capable of performing increasingly complex tasks in the gut, it is necessary to harness the ability of the microbiota to communicate in the gut environment.  However, little is known about how all these different strains of bacteria communicate with each other in a process known as quorum sensing, a bacterial information transfer system, and whether it is possible to develop the types of signaling pathways responsible for enabling the flow of information between them.  Now, a study led by researchers at Harvard University engineers a genetic signal-transmission system where molecular signals 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, successfully mimicking the quorum sensing process.  The team states their data brings the global medical community a step closer to developing a synthetic microbiome composed of bacteria programmed to perform specific functions. The study is published in the journal ACS Synthetic Biology.

Previous studies show bacteria are routinely genetically engineered, with the hope of tweaking the genes of these intestinal interlopers to do more than just help digest food.  The main desire is to develop a synthetic microbiome with the ability to record information about the state of the gut in real-time whilst reporting the presence of disease or suspicious activity.  However, bacterial quorum sensing has not yet been identified in the 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 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 the signaler circuit contains a single copy of a gene called luxI activated by the molecule anhydrotetracycline (ATC) known to produce a quorum-sensing signaling molecule. Data findings show when the signaling molecule binds to the responder circuit a gene called cro is activated to produce the protein Cro, which in turn switches on a memory element within the responder circuit. This memory element expresses LacZ designed to turn the bacterium blue when plated on a special agar, thus producing visual confirmation the signal molecule has been received.

Results show 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 all mice display signs of signal transmission, confirming the engineered circuits allowed communication between different species of bacteria in the complex environment of the mammalian gut.

The team surmises 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 consisting of engineered bacteria species with distinct and specific functions within the human gut.

Source: Wyss Institute for Biologically Inspired Engineering 

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