05 September 2018

Phone for microflora

Biologists have taught genetically modified intestinal bacteria to communicate with each other

Anatoly Glossev, Vesti

Scientists have created intestinal bacteria capable of exchanging special chemical signals with each other. In the future, researchers hope to create an artificial microbial community that will monitor human health and perform other functions. The achievement is described in a scientific article published in the journal ACS Synthetic Biology by a group led by Pamela Silver from Harvard Medical School.

Biologists are well aware that bacteria are able to "confer" with each other by releasing certain chemicals (although there are other ways). This allows them, for example, to decide that the conditions are now unfavorable and it's time to fall into "hibernation". Experts call this channel of information transmission a sense of quorum.

Such chemical communication allows some microbes to assemble into complex aggregates comparable in their properties to multicellular organisms. It would be tempting to create such an artificial microbial community with the necessary parameters and functions. Or, say, to remake the gut microbiome at your discretion, so that its inhabitants bring less harm and more benefit.

This idea inspired the authors to create genetically modified intestinal bacteria capable of transmitting messages "programmed" by genetic engineers to each other. At the same time, biologists used a chemical signal that has never been observed in the intestinal microbiome of mammals.

Firstly, it allowed us to fully test the potential of genetic engineering in this matter. The researchers wanted to find out whether it would be possible to "teach" intestinal bacteria what they had never "been able to do." Secondly, the use of an unusual chemical pathway ensured that the "receiver" would not react to extraneous signals.

At the first stage of the experiment, scientists derived two lines of E.coli coli: one of them were "receivers", the other – "transmitters". The first, having found anhydrotetracycline (AGTC) molecules in the environment, produced acyl-homoserinlactone. The latter substance served as a chemical signal for the latter.

The "receivers", having received the messages, activated a gene that made the bacterial shells blue. This gene remained "on" even when the concentration of the signaling substance fell below the threshold value. Thus, the "receiver" bacterium was equipped with a kind of memory. This ensured that the researchers would be able to isolate the bacteria that received the signal even after a long time.

The authors tested this system "in vitro" and made sure that the "receivers" turn blue when the "transmitters" receive the AGTC. After that, biologists decided to check whether it would be possible to transmit such messages between different strains of bacteria. They left E.coli as the "receiver", and made Salmonella typhimurium the "transmitter", building the same system in its genome as before in E.coli. Interspecific communication worked no worse than intraspecific communication.

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Finally, the experimenters planted "talkative" E.coli bacteria (both "receivers" and "transmitters") in the intestines of live mice. Rodents received portions of AGTC with water for two days. Analysis of their feces confirmed that the "receivers" turned blue safely. That is, the system worked in the intestines of the animal.

In the future, the authors hope to expand the range of bacteria and chemical signals used.

"Ultimately, we aim to create a synthetic microbiome in our gut, consisting entirely or predominantly of [genetically] engineered bacterial species, each of which has a specialized function, for example, the detection and treatment of diseases, the creation of beneficial molecules, improving digestion, and so on. At the same time, he [the species] communicates with others so that they are all balanced in order to best ensure human health," Silver says.

However, such a goal cannot be called close. "Vesti.Science" (nauka.vesti.ru ) we have already written that half of the bacteria in the human intestine is simply not known to science. At the same time, biologists are discovering more and more new aspects of their interaction with the human body. For example, it turned out that they influence the development of many diseases and control our genes, and perhaps, to some extent, consciousness. Interference in such a complex and little-studied system can threaten unpredictable consequences. Therefore, scientists will have to measure not even seven times, but seventy times seven, before they "cut off" at least some part of their natural microbiome from a person.

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