A research group led by scientists from the University of São Paulo (USP) in São Carlos, Brazil, has identified a series of bioactive compounds in a marine sponge collected in Fernando de Noronha, an archipelago about 400 km off the coast of northeastern region of Brazil. . Some of the substances have been shown to be able to kill antibiotic-resistant bacteria currently available, paving the way for the development of new drugs.
The study was supported by FAPESP and was reported in an article published in the Journal of Natural Products.
“This marine sponge had been previously studied by groups outside Brazil, mainly in the 1990s. We used next-generation techniques to analyze substances of their secondary metabolism, look for new molecules and test their biological activity. We were able to describe a series The main potential detected was against drug-resistant bacteria, “said Vítor Freire, who conducted the study as part of his doctoral research at the Instituto de Química de São Carlos (IQSC- USP).
The World Health Organization (WHO) considers antibiotic resistance to be a major global public health problem. According to a report commissioned by the British government and published in 2016, deaths from drug-resistant bacterial infections are expected to reach 10 million a year by 2050. Hence the importance of discovering new effective antibiotics.
The marine sponge analyzed in the study is Agelas dispar, a species native to the Caribbean and part of the Brazilian coast. Marine sponges are among the oldest organisms on Earth and spend their lives anchored on reefs or the seabed. In millions of years of evolution, they have developed a complex metabolism, producing substances needed to compete with other invertebrates and prevent infection by pathogenic bacteria.
The substances with the most therapeutic potential identified in the study were three different types of ageliferin, named after the genus Agelas marine sponges.
“Another important factor is the ability of sponges to store symbiotic microorganisms, which also help them defend themselves. When we analyze the compounds found in sponges, we don’t always know what they have produced and what comes from the symbionts,” he said. dir Roberto Berlinck. , professor at the IQSC-USP and principal investigator of the study.
The research has been carried out in the framework 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, the FAPESP Research on Characterization, Biodiversity Conservation, Restoration and Sustainable Use).
The tests with bacteria were carried out 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 in an ovarian cancer cell line known as OVCAR3, but were not found to be biologically active. Other research groups that tested ageliferins in lung, colon, and breast cancer cells observed no antitumor action and one had no effect on lymphoma cells. However, three ageliferins eliminated bacteria resistant to the drugs 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 lethal side effect that is often seen in patients undergoing chemotherapy who need antibiotics. In murine cells, the compounds did not cause this type of damage, suggesting a promising potential for drug development.
The next step is to analyze other marine sponges using the same methodology. “Finding out how these substances are produced is extremely important, as they are distributed across various classes of sponges and could help treat diseases in the future,” said Freire, currently a postdoctoral researcher at the U.S. National Cancer Institute.
The study also had the support of FAPESP through scholarships awarded to Juliana Gubiani for postdoctoral research at the IQSC-USP and Erica de Castro Levatti for postdoctoral research at the IAL.
Source:
São Paulo Research Foundation (FAPESP)
Magazine reference:
10.1021 / acs.jnatprod.2c00094