Scientists explore ant microbiota in search of new drugs

Project brings together researchers from the University of São Paulo and Harvard University and was approved in the first joint call for proposals launched by FAPESP and the NIH.

By Karina Toledo

Agência FAPESP – As residents of large cities know very well, environments with large clusters of individuals are ripe for the spread of pathogens and therefore require special attention to prevent diseases.

Just as we humans depend on vaccines, medicines and disinfectants to protect ourselves, social insects – such as bees, ants and termites – have developed their own “chemical weapons” over thousands of years of evolution, and these are now being explored by science.

“One of the strategies used by insects that live in colonies is association with symbiotic microorganisms – mostly bacteria – capable of producing chemical compounds with antibiotic and antifungal action,” said Monica Tallarico Pupo, a professor at the Ribeirão Preto School of Pharmaceutical Sciences (FCFRP) of the University of São Paulo (USP).

In a project recently approved during the first joint call for proposals launched by FAPESP and the United States National Institutes of Health (NIH), the Pupo team will join the group led by Jon Clardy at Harvard University to explore the microbiota found in the bodies of Brazilian ants in search of natural molecules that could give rise to new drugs.

“We’re going to begin by focusing on leaf-cutting ants like the sauba because they have the symbiotic relationship most extensively described in the scientific literature,” said Pupo.

According to the researcher, leaf-cutting ants behave similarly to actual farmers, carrying pieces of plants into their nests to nourish the cultures of fungi on which they feed. “This creates a nutrient-rich environment susceptible to attack by opportunistic microorganisms. To maintain the health of the anthill, it is important to have the associated symbionts,” Pupo explained.

The researchers will embark on a hunt for ants in national parks located in several Brazilian biomes, such as the Cerrado, the Atlantic Forest, the Amazon and the Caatinga. Also part of the collection area is Vassununga State Park, in the municipality of Santa Rita do Passa Quatro in the state of São Paulo.

The group’s goal is to isolate nearly 500 lineages of bacteria per year, which they estimate will give rise to 1,500 different extracts. “The first step will be to collect insects and nest fragments for laboratory analysis. We’ll then isolate the existing lineages of bacteria and use morphology and DNA sequencing methods to characterize the microorganisms,” Pupo explained.

After the bacteria have been properly preserved and cataloged, the researcher added, it will be possible to cultivate the lineages and then extract the growth medium. “We estimate that each lineage will give rise to three different extracts, depending upon the nutrient used in the culture and the extraction technique selected,” she said.

These extracts will be tested in vitro to determine whether they are capable of inhibiting the growth of fungi, cancer cells and cells from the parasites that cause leishmaniasis and Chagas disease. The active components of the most promising of these will be isolated and studied more extensively.

“It is common for this type of study to be redundant: in other words, to isolate compounds already known in the literature. In order to streamline the discovery of new active substances, we’ll use dereplication and genomic sequencing tools,” Pupo said.

The team will also include bacteriologist Cameron Currie (University of Wisconsin-Madison), Fabio Santos do Nascimento (USP Riberão Preto Faculty of Philosophy, Science and Languages and Literature), André Rodrigues (São Paulo State University in Rio Claro), Adriano Defini Andricopulo (USP São Carlos Institute of Physics), James E. Bradner (Dana-Farber Cancer Institute of Harvard Medical School), Timothy Bugni (University of Wisconsin-Madison) and David Andes (University of Wisconsin-Madison).

The FAPESP/NIH call for proposals is associated with the International Biodiversity Cooperative Groups (ICBG) program, which Brazil is participating in for the first time.

Beginnings

According to Pupo, the collaborative project is an extension of work that had been performed under a regular research award approved in mid-2013, which also involved collaboration by Clardy and Currie.

“We’re studying species of bees [Scaptotrigona depilis] and ants [Atta sexdens] found on the Ribeirão Preto campus of USP. In this case, we’re exploring the insects’ entire microbiota, including bacteria and fungi, and certain isolated compounds are indicating quite marked antifungal and antibacterial potential,” she explained.

The study is being performed as part of the doctoral work of Eduardo Afonso da Silva Júnior and Camila Raquel Paludo, both FAPESP scholarship recipients. Also participating is undergraduate scholarship recipient Taise Tomie Hebihara Fukuda.