A research group 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 on Fernando de Noronha, an archipelago about 400 km off the coast of the northeastern region. from Brazil . Some substances were found to be able to kill bacteria resistant to current antibiotics, paving the way for the development of new drugs.
The study was supported by FAPESP and reported in an article published in the Journal of Natural Products †
“This sea sponge had previously been studied by groups outside of Brazil, mainly in the 1990s. We used next-generation techniques to analyze substances from secondary metabolism, find new molecules and test biological activity. We were able to describe some of the new compounds. The main potential detected was against 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 from infections from resistant bacteria will reach 10 million a year by 2050. Hence the importance of discovering effective new antibiotics.
The sea sponge analyzed in the study is: Agelas dispar, a species native to the Caribbean and part of the Brazilian coast. Sea sponges are among the oldest organisms on Earth and spend their lives anchored to reefs or the seabed. Over millions of years of evolution, they have developed a complex metabolism, producing substances necessary 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 of the sea sponges. Agelas †
“Another important factor is the ability of sponges to store microorganisms from symbionts, which also helps them defend themselves. When we analyze compounds in sponges, we don’t always know what’s produced by them and what comes from symbionts.” said Roberto Berlinck, a professor at IQSC-USP and principal investigator for the study.
The research was conducted 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, the FAPESP Research Program on Biodiversity Characterization, Conservation, Restoration and sustainable use).
The bacteria trials were conducted 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 found not to be biologically active. Other research groups testing ageliferins on lung, colon and breast cancer cells observed no antitumor activity and one had no effect on lymphoma cells. However, three ageliferins eliminated resistant bacteria Escherichia coli and Enterococcus faecalis, which are very common and found in various environments and 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 one of the bacteria responsible for most hospital-acquired infections.
The researchers wanted to know whether taking these ageliferins could lead to destruction of red blood cells (hemolysis) in the gut, a potentially fatal side effect often seen in patients undergoing chemotherapy who need antibiotics. In mouse cells, the compounds did not cause this type of damage, suggesting promising potential for drug development.
The next step is to analyze other marine sponges using the same method. “It is extremely important to find out how these substances are produced, because they are spread by different types of sponges and could help in the treatment of diseases in the future,” said Freire, currently a postdoctoral researcher at the National Cancer Institute in the United States. States.
The study was also supported by FAPESP through grants awarded to Juliana Gubiani for postdoctoral research at IQSC-USP, and Erica de Castro Levatti for postdoctoral research at IAL.
Source:
Sao Paulo Research Foundation (FAPESP)
Reference magazine:
10.1021/acs.jnatprod.2c00094