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Argentine biotechnologists edited the cholera genome to reduce its proliferation

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Researchers from the National University of San Martín (UNSAM) developed a technique to edit the genome of two bacteria, with the aim of reprogramming their rate of proliferation. Specifically, they are working on a technology that seeks to reduce the growth of cholera and, on the other hand, accelerate the growth of bacteria that benefit soybean production.

“We find that for a gene carry out its function, it is not only necessary to take into account its presence or absence in the genome, but also the physical place it has in the genome and the conjunction that occurs with the rest of the genes. In other words, it depends on where the instrument is located to see how the orchestra plays”, he explained to TechMarkup Alfonso Solerwho leads this research within the university’s Biotechnological Research Institute. The rest of the team is made up of Leticia Larotonda, Ian Medici, Federico Paez Córdoba, Belén Bordignon and Leila Bartrolí.

Soler says that The research group has been working to understand why some bacteria replicate very quickly, in a few minutes, as occurs with cholera; and others take weeks to divide. Starting from this base, modifications were sought to alter its reproduction rhythm. In other words, research focuses on genomic reprogramming of bacterial growth.

“We move key genes and see that the further we move them from their original site, the slower they grow. By doing several similar experiments, relocating the same genes to three or four different places, we managed to generalize the phenomenon mathematically. Finally, we can predict what the growth rate will be depending on where the gene is located”, explained Soler.

The technology goes through this entire research process, since genetic editing techniques are used to rearrange and change the location of genes. The big data is also present because it is done data mining, to process all the information that is produced by massive sequencing techniques.

The potential usefulness of this biotechnological discovery is that in the case of a pathogen, such as the cholera bacterium, it reprograms the growth of the pathogen by gene relocation so that it reproduces more slowly and therefore slows down the bacterium’s infectivity. It could also be the kick to develop a vaccine against this disease that, according to the WHO, causes between 21,000 and 143,000 deaths per year and infects around 3 million people.

“A prototype has been created, which was tested on flies, but there is still a long way to go to generate a prototype for humans. The idea is to prove the concept: if a microorganism that grows slower is created, it can generate the same immune response but without infecting. In the very long term, the idea is to develop a vaccine against cholera”, analyzed Soler. It could also be the beginning of a technique that could be used to develop vaccines against other pathogens.

On the other hand, they have used this technique to achieve the opposite effect: to make a bacterium, which has a positive use for the soil and that grows slowly, increase its growth rate.

“This is the case of the Bradyrhizobium bacterium, which is used as an inoculant in the field and which generates an infection that benefits the plant, makes it develop better. This bacterium, unlike what happens with cholera, takes 20 hours to divide. The idea is to reduce that time. We want to accelerate this growth to see if we can make a bradyrhizobium that grows faster and facilitates the production of inoculants, which help reduce the amount of fertilizers used and the pollution they generate in the environment,” said the specialist.

In relation to this experiment, he explains that they have already developed a first prototype of bradyrhizobium, which instead of dividing into 20 hours, divides into 5 or 6 hours. The next step is to test it on plants.

The group was supported by an international grant of 55 thousand euros from the International Center for Genetic Engineering and Biotechnology (ICGEB, International Center for generic Engineering and Biotechnology) of Trieste and another from Ecos Sud, a scientific cooperation initiative to intensify relations between research centers and universities in Argentina and France. Last December they also received support from the National Agency for the Promotion of Research, Technological Development and Innovation for $11,000,000.

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