NOTICIAS DIARIAS

Genetic Engineering to Create Synthetic Microbiome

Microbiology

What if the bacteria that live in your gut could monitor your health, report disease, and produce beneficial molecules? Researchers have gotten one step closer to creating such a 'synthetic microbiome' by engineering different species of bacteria so they can talk to each other. Given that there are over 1,000 different strains of intestinal interlopers in the human gut, such coordination is crucial for the development of systems that can sense and improve human digestive health.

Researchers have successfully engineered 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, bringing scientists a step closer to developing a "synthetic microbiome" composed of bacteria that are programmed to perform specific functions. The study is reported in ACS Synthetic Biology.

"In order to improve human health through engineered gut bacteria, we need to start figuring out how to make the bacteria communicate," said Suhyun Kim. "We want to make sure that, as engineered probiotics develop, we have a means to coordinate and control them in harmony."

Quorum sensing

The team harnessed an ability that naturally occurs in some strains of bacteria called "quorum sensing," in which the bacteria send and receive signal molecules that indicate the overall density of the bacterial colony and regulate the expression of many genes involved in group activities.

A particular type of quorum sensing known as acyl-homoserine lactone (acyl-HSL) sensing has not yet been observed in the mammalian gut, so the team decided to see if they could repurpose its signaling system to create a bacterial information transfer system using genetic engineering.

The researchers introduced two new genetic circuits into different colonies of a strain of E. coli bacteria: a "signaler" circuit, and a "responder" circuit. 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.

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 two additional genes: LacZ and another copy of cro.

Expression of LacZ

The expression of LacZ causes the bacterium to turn blue if plated on a special agar, thus producing visual confirmation that the signal molecule has been received. The extra copy of cro forms a positive feedback loop that keeps the memory element on, ensuring that the bacterium continues to express LacZ over an extended period of time.

Finally, the team repeated the in vivo experiment, but gave the mice signaler S. Typhimurium bacteria and E. coli responder bacteria, to see if the signal could be transmitted across different species of bacteria within the mouse's gut. All mice displayed 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 researchers hope to continue this line of inquiry by engineering more species of bacteria so that they can communicate, and by searching for and developing other signaling molecules that can be used to transmit information between them.

"Ultimately, we aim to create a synthetic microbiome with completely or mostly engineered bacteria species in our gut, each of which has a specialized function but also communicates with the others to ensure that they are all balanced for optimal human health," said corresponding author Silver. 

"The microbiome is the next frontier in medicine as well as wellness. Devising new technologies to engineer intestinal microbes for the better while appreciating that they function as part of a complex community, as was done here, represents a major step forward in this direction," said Wyss Founding Director Donald Ingber.