A research team led by researchers at the University of São Paulo (USP) in São Carlos, Brazil, has identified a number of bioactive compounds in a marine fungus collected on Fernando de Noronha, an archipelago about 400 km off the coast of Brazil’s northeastern region. . Some of the drugs were shown to be able to kill bacteria that are resistant to currently available antibiotics, paving the way for the development of new drugs.
The study was supported by FAPESP and reported in an article published in Journal of Natural Products.
“This marine fungus had previously been studied by groups outside Brazil, mainly in the 1990s. We used next-generation techniques to analyze substances from its secondary metabolism, look for new molecules, and test its biological activity. We were able to describe a number of new compounds. The greatest potential discovered was against drug-resistant bacteria, “said Vítor Freire, who conducted the study as part of his PhD research at the São Carlos Institute of Chemistry (IQSC-USP). .
Antibiotic resistance is considered a major global public health problem by the World Health Organization (WHO). According to a report commissioned by the UK government and published in 2016, deaths due to infections with drug-resistant bacteria are set to reach 10 million a year by 2050. Therefore, it is important to discover effective new antibiotics.
The marine fungus analyzed in the study is Agelas dispar, a species native to the Caribbean and part of the Brazilian coast. Marine fungi are among the oldest organisms on Earth and spend their lives anchored to reefs or the ocean floor. In millions of years of evolution, they have developed a complex metabolism that produces substances necessary to compete with other invertebrates and to avoid infection with pathogenic bacteria.
The substances with the most therapeutic potential identified in the study were three different types of ageliferin, named after the marine fungal genus Agelas.
“Another important factor is the ability of fungi to store symbiont microorganisms, which also help them defend themselves. When we analyze compounds found in fungi, we do not always know what has been produced by them and what comes from symbionts. , “says Roberto Berlinck. , professor at IQSC-USP and lead investigator for the study.
The research was carried out as part of two projects led by Berlinck and supported by FAPESP (grants 19 / 17721-9 and 13 / 50228-8, the latter under the auspices of BIOTA-FAPESP, FAPESP Research Program on Biodiversity Characterization, Conservation, Restoration and Sustainable use).
The experiments involving bacteria were performed at the Adolpho Lutz Institute (IAL), the reference laboratory for epidemiological surveillance in the state of São Paulo, and led by André Gustavo Tempone, a researcher also supported by FAPESP.
Tumors and bacteria
Thirteen compounds were tested on an ovarian cancer cell line known as OVCAR3 but were not found to be biologically active. Other research groups testing ageliferins on lung, colon, and breast cancer cells did not observe antitumor activity, and one had no effect on lymphoma cells. However, three ageliferins eliminated drug-resistant bacteria Escherichia coli and Enterococcus faecalis, which are extremely common and are found in various environments as well as in the human body; and Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, listed by the WHO as priority targets for new antibiotics and among the bacteria responsible for most hospital-acquired infections.
The researchers wanted to know if the use of these ageliferins could lead to the destruction of red blood cells (hemolysis) in the intestines, a potentially fatal side effect often seen in patients undergoing chemotherapy and needing antibiotics. In murine cells, the compounds did not cause this type of damage, suggesting promising drug development potential.
The next step is to analyze other marine fungi using the same method. “Finding out how these drugs are produced is extremely important as they are distributed by several classes of fungi and may help treat diseases in the future,” said Freire, who is currently a postdoc researcher at the National Cancer Institute in the United States. .
The study was also supported by FAPESP through scholarships awarded to Juliana Gubiani for postdoctoral research at IQSC-USP, and Erica de Castro Levatti for postdoctoral research at IAL.
Source:
São Paulo Research Foundation (FAPESP)
Journal reference:
10.1021 / acs.jnatprod.2c00094