A research team led by scientists from the University of São Paulo (USP) in São Carlos, Brazil, has identified a number of bioactive compounds in a sea sponge collected from Fernando de Noronha, an archipelago about 400 km off the coast of Brazil’s northeast region. . Some of the substances have been shown 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 is described in an article published in Journal of Natural Products.
“This sea sponge was previously studied by groups outside of Brazil, mostly in the 1990s. We used next-generation methods to analyze substances from its secondary metabolism, search for new molecules, and test its biological activity. We have been able to describe a number of new compounds. The main potential found was against drug-resistant bacteria,” said Vitor Freire, who conducted the research as part of his doctoral dissertation at the San Carlos Institute of Chemistry (IQSC-USP).
The World Health Organization (WHO) considers antibiotic resistance a major global public health problem. According to a report commissioned by the British government and published in 2016, deaths from infections caused by drug-resistant bacteria will reach 10 million a year in 2050. Hence the importance of discovering effective new antibiotics.
The sea sponge analyzed in the study, Agelas dispar, a species native to the Caribbean and parts of the Brazilian coast. Sea sponges are among the oldest organisms on earth and spend their lives anchored off reefs or on the seafloor. Over millions of years of evolution, they have developed a complex metabolism, producing the substances necessary to compete with other invertebrates and to prevent infection by pathogenic bacteria.
The substances with the greatest therapeutic potential identified in the study were three different types of ageliferin, named after a genus of marine sponges. Agelas.
“Another important factor is the ability of sponges to accumulate symbiotic microorganisms, which also help them defend themselves. When we analyze the compounds found in sponges, we don’t always know what they produced and what comes from the symbionts,” said Roberto Berlink. , IQSC-USP professor and principal investigator of the study.
The study was carried out in two projects led by Berlink and supported by FAPESP (grants 19/17721-9 and 13/50228-8, the latter under the auspices of BIOTA-FAPESP, the FAPESP Research Program for Biodiversity Characterization, Conservation, Restoration and Sustainable Use).
Tests involving bacteria were carried out at the Adolfo Lutz Institute (IAL), a reference laboratory for epidemiological surveillance in the state of São Paulo, under the direction of André Gustavo Tempone, a researcher also supported by FAPESP.
Tumors and bacteria
Thirteen compounds were tested in the ovarian cancer cell line known as OVCAR3, but no biological activity was found. Other research groups that tested ageliphrines on lung, colon, and breast cancer cells found no antitumor activity, and one had no effect on lymphoma cells. However, the three agelifins killed drug-resistant bacteria. coli as well as Enterococcus fecalis, which are extremely common and found in various environments, as well as in the human body; as well as Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii as well as Pseudomonas aeruginosa, included in the WHO list of priority targets for new antibiotics and among the bacteria responsible for most nosocomial 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 often occurs in patients undergoing chemotherapy and requiring antibiotics. In mouse cells, the compounds did not cause this kind of damage, suggesting promising drug development potential.
The next step is to analyze other marine sponges using the same methodology. “Understanding how these substances are produced is extremely important as they are distributed among several classes of sponges and could help treat diseases in the future,” said Freire, who is currently working on his doctoral dissertation at the National Cancer Institute in the United States.
The research was also supported by FAPESP through fellowships awarded to Giuliana Gubiani for postdoctoral research at IQSC-USP and Erika de Castro Levatti for postdoctoral research at IAL.