Novel compounds discovered in marine sponge can kill drug-resistant bacteria

A research group led by scientists at the University of São Paulo (USP) in São Carlos, Brazil, has identified a number of bioactive compounds in a marine sponge collected on Fernando de Noronha, an archipelago located about 400 km off the coast of Brazil's northeastern region. Some of these substances were found to be capable of killing bacteria resistant to currently available antibiotics, paving the way for the development of new drugs.

The study was supported by FAPESP and is the subject of an article published in the Journal of Natural Products.

"This marine sponge had been studied before by groups outside Brazil, mainly in the 1990s. We used next-generation techniques to analyze substances from its secondary metabolism, search for new molecules and test its biological activity. We were able to describe a number of new compounds. The main potential detected was against drug-resistant bacteria," said Vítor Freire, who conducted the study as part of his doctoral research at the São 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 with drug-resistant bacteria are expected to reach 10 million per 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 to reefs or the sea floor. Over millions of years of evolution, they have developed a complex metabolism, producing substances necessary to compete with other invertebrates and to avoid infection by pathogenic bacteria.

The substances with the greatest therapeutic potential identified in the study were three different types of ageliferin, named after the marine sponge genus Agelas.

"Another important factor is the ability of sponges to store symbiont microorganisms, which also help them defend themselves. When we analyze the compounds found in sponges, we don't always know what was produced by them and what came from the symbionts," said Roberto Berlinck, a professor at IQSC-USP and lead researcher of the study.

Thirteen compounds were tested on an ovarian cancer cell line called OVCAR3, but they were not found to be biologically active. Other research groups that tested ageliferins on lung, colon and breast cancer cells did not observe any antitumor action, and one had no effect on lymphoma cells. In contrast, three ageliferins eliminated drug-resistant bacteria, namely Escherichia coli and Enterococcus faecalis, which are extremely common and found in a variety of environments as well as in the human body, and Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which are on the WHO's list of priority targets for new antibiotics and are among the bacteria responsible for most hospital 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 who require 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. "It is extremely important to find out how these substances are produced, as they are distributed by several classes of sponges and could help treat diseases in the future," said Freire, currently a postdoctoral researcher at the National Cancer Institute in the United States.