Scientists at the University of California, San Diego, have successfully created a genetically engineered E. coli found in the gut microbiomes of mice and humans. Both bacteria have demonstrated their potential to treat diseases like diabetes.
E. Coli Modification Through Genetic Engineering
The initiative on modifying the bacteria was previously concentrated on engineering common lab strains of E. coli, which are unable to compete with the gut bacteria that are already present and have adapted to their host. The gut microbiome is very dynamic and constantly changing, making things even more difficult for the non-native bacteria, according to the senior author of the paper and gastroenterologist Amir Zarrinpar at UC San Diego Health.
With all of these hostile environments designed to stop bacterial invaders from taking root, it is difficult for bacteria that have never lived inside a mammal before to now enter the gut microbiome jungle. The team devised a solution by directly engineering E. coli collected from the hosts.
The bacteria in our bodies are customized for each individual based on the types of foods we eat, the typical stresses our bodies undergo or produce, and our genetic make-up. Native bacteria have a big advantage because this constantly changing environment is normal. This makes them excellent candidates for engineering.
According to Zarrinpar, these bacteria have been modified to function as factories that can produce medicines which could live in our microbiome.
“We have engineered these bacteria to become factories that can live in our microbiome and potentially produce medicines,” Zarrinpar said, EurekAlert! reported. “We know that E. coli can pick up pathogenic genes and cause disease, and now we're just realizing that if we put a beneficial gene in, it can help us to treat chronic diseases, maybe even cure some of them.”
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Laboratory Procedure in Modifying E. Coli
Before extracting E. coli, the team first took stool samples from the host for additional alterations.
"We say to the bacteria: Hey, we will give you a new superpower," said Zarrinpar.
The so-called superpower the bacteria received is the protein bile salt hydrolase (BSH).
The E. coli with BSH spread throughout the entire gut of the mice after a single treatment, and they maintained their BSH activity for the rest of the host's life. The study showed how BSH activity could prevent mice from developing diabetes.
It is a vast improvement over similar treatments using laboratory strains of engineered bacteria that are non-native, where multiple treatments are frequently necessary. Additionally, these artificial bacteria do not persist in the host's gut as long or as frequently as the natural E. coli technique discovered by Professor Zarrinpar's group. In addition to successfully influencing diabetes in mice, the team was able to modify E. coli removed from a human gut.
As a natural defense mechanism, native bacteria are very resistant to modifications. We can now more effectively engineer these bacteria thanks to a variety of new genetic engineering tools. Zarrinpar and his team are improving this procedure. Still, their data indicate that introducing a gene into a native bacterium has a 100-fold lower success rate than doing so with lab strain bacteria.
The ability to more effectively engineer these bacteria is now possible thanks to a variety of new genetic engineering tools. The team hopes to use this technology to identify new diseases that can be treated. The technology can potentially open up the application of microbiome therapy.
The researchers published the study in the journal Cell.
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