Research on bacteria in the Amazon could develop new medicines

By Guilherme Jeronymo, Reporter for Agência Brasil - Part of Brazil's cutting-edge drug research involves taking soil samples from Belém (PA) to a laboratory complex larger than a football stadium in Campinas, in the interior of São Paulo state. This entire journey is to place microscopic organisms in what is, roughly speaking, the largest microscope in South America, the Sirius accelerator, part of the National Center for Research in Energy and Materials (CNPEM). With this tool, it is possible to understand how bacterial genes work and what substances they can create. The teams involved are searching for substances with antibiotic and antitumor potential, and the first results were published in December in a... international specialized magazine.

The reason for this journey into the Amazonian soil is the partnership between CNPEM and the Federal University of Pará (UFPA). The fieldwork began by collecting soil samples from the interior of the Utinga State Park, a conservation reserve established in 1993 that includes restored areas and areas without recent human intervention. The group investigated three bacterial species from the classes Actinomycetes e Bacilli isolated from Amazonian soil, comprising bacteria of the genus Streptomyces, Rhodococcus and Brevibacillus.

The next step occurred when researchers at the EngBio laboratory at UFPA, led by Diego Assis das Graças, used the PromethION sequencer from Oxford Nanopore (United Kingdom), "which stands out for generating high-quality reads, allowing the sequencing of complex genomes with high data throughput and low cost. Nanopore-based sequencing technology allows for real-time analysis and direct DNA reading. Furthermore, its portability and flexibility make it suitable for laboratory and field applications," explained Diego, who is one of the authors of the first article written from this phase of the research.

With this sequencing, it was possible to examine genes and understand how they act in the construction of enzymes, and the pathways that make them more complex molecules. Half of these were previously unknown.

"These molecules are the focus of our studies, as they are of great importance for the development of drugs and medicines. For example, more than 2/3 (two thirds) of all drugs developed in the world originate from small natural molecules, secondary metabolites or specialized metabolites," explained researcher Daniela Trivella, coordinator of Drug Discovery at LNBio (National Laboratory of Biosciences).

The data analysis was also conducted at LNBio using Sirius. This sequencing is much more accessible, in terms of cost and time, than it was a decade or two ago. With this, it's possible to analyze what Trivella explained as "wild" bacteria, that is, those found in nature. Current estimates suggest that less than 1 in 10 species of wild bacteria can be cultivated in the laboratory, and when they can, less than 10% of the genes they carry are expressed in the lab. All the rest is "lost" to science without these cutting-edge methods. "So, there are many bacteria that we still don't know and many natural products that we couldn't produce in the laboratory, or could produce in very low yields," Daniela added.

In short, location matters, a lot. "Clusters of biosynthetic genes are responsible for the production of substances with biological potential, such as medicines. Even in organisms already studied, such as bacteria of the genus Streptomyces"We saw that there are still many unknown substances in specimens isolated from Amazonian soil. This shows how essential the ecosystem is for new discoveries. The Amazon, in this sense, remains a rich and underexplored area for developing new products," said another participant, researcher Rafael Baraúna (EngBio-UFPA), who coordinated the work for UFPA, in a statement.

The final step was to scale up production to a laboratory level. By understanding which genes produce each substance, using an advanced technique called metabologenomics, the researchers "convinced" commonly managed laboratory bacteria species to accept these genes and produce the substances in quantities that can be tested and worked with. "With the target coding DNA, the domesticated bacteria, which did not produce the metabolite of interest, begins to produce it, because it artificially received the DNA sequence that we saw in the forest. Thus, we have access to this molecule to develop new drugs from it. In other words, access to new molecules through a biotechnological route," said Trivella.

This set of tests doesn't isolate just one or two molecules. With the entire CNPEN structure, a dedicated laboratory like LNBio can perform up to 10 tests in a single day. This speed competes with another, voracious one: the speed of devastation. The year 2024 saw the highest number of wildfires in the Amazon in the last 17 years. To try to help in this race, from the scientific side, investments in research in the biome were announced at the last meeting of... Brazilian Society for the Progress of Science (SBPC) are at the level of R$ 500 million this decade, with the potential to help economically enhance the territory and its original coverage. 

Since some of the targets are molecules to treat infections and tumors, the return on investment has the potential to exceed the investment. "All these methods are condensed in the LNBio-CNPEM Drug Discovery Platform. This platform conducts research on new drugs, ranging from the preparation of chemical libraries of biodiversity and the selection of therapeutic targets for drug development, to obtaining the prototype molecule (the invention), which then goes through regulatory stages to reach industrial production and patients in the clinic," illustrates Trivella. According to her, the next phases of the research will take the field teams far from Belém, to the eastern Amazon. There they hope to confirm the immense potential of new molecules from the biome and begin to understand it even better.

This work is part of a larger effort to create a multi-user research center at UFPA, supported by CNPEM and national projects such as Iwasa'i, recently implemented in the context of the CNPq/MCTI/FNDCT Call for Proposals No. 19/2024 - Advanced Centers in Strategic Areas for the Sustainable Development of the Amazon Region - Pró-Amazônia.